biomolecules

Review
Mechanical Properties and Functions of Elastin: An Overview
Hanna Tr˛ebacz * and Angelika Barzycka

Department of Biophysics, Medical University of Lublin, Al. Racławickie 1, 20-059 Lublin, Poland
* Correspondence: [email protected]

Abstract: Human tissues must be elastic, much like other materials that work under continuous loads
without losing functionality. The elasticity of tissues is provided by elastin, a unique protein of the
extracellular matrix (ECM) of mammals. Its function is to endow soft tissues with low stiffness, high
and fully reversible extensibility, and efficient elastic–energy storage. Depending on the mechanical
functions, the amount and distribution of elastin-rich elastic fibers vary between and within tissues
and organs. The article presents a concise overview of the mechanical properties of elastin and
its role in the elasticity of soft tissues. Both the occurrence of elastin and the relationship between
its spatial arrangement and mechanical functions in a given tissue or organ are overviewed. As
elastin in tissues occurs only in the form of elastic fibers, the current state of knowledge about
their mechanical characteristics, as well as certain aspects of degradation of these fibers and their
mechanical performance, is presented. The overview also outlines the latest understanding of the
molecular basis of unique physical characteristics of elastin and, in particular, the origin of the driving
force of elastic recoil after stretching.

Keywords: elastic fiber; elastic recoil; mechanical properties; soft tissues

1. Introduction
The mechanical role of tissues is to deliver an appropriate physical response to forces,
both resulting from organ physiology and being due to external loads the body is subjected
to. In order to ensure an optimal response, each tissue with defined mechanical func-
Citation: Tr˛ebacz, H.; Barzycka, A. tions should provide sufficiently strong structural support in addition to being properly
Mechanical Properties and Functions deformable. The reversible deformability of the extracellular matrix (ECM) of tissues is
of Elastin: An Overview. Biomolecules essential for the functioning of many organs, including the lungs, skin, and blood vessels.
2023, 13, 574. https://doi.org/ In a physical meaning, any material is elastic if it is able to return to its original shape
10.3390/biom13030574 and size after deformation when the force of deformation is removed. Human tissues must
be elastic like all other materials designed to work under a load for a long time and without
Academic Editor: Vladimir
N. Uversky
losing functionality. Although the physical meaning of elasticity does not imply high
deformability, soft tissues are both elastic and stretchy, i.e., they can be largely deformed
Received: 14 February 2023 when a little force has been exerted. This elastomeric elasticity is provided by elastin, the
Revised: 8 March 2023 only protein possessing this feature in mammals [1,2]. Elastin also has the ability to store
Accepted: 20 March 2023 elastic–strain energy with almost perfect efficiency and is extremely durable [3–6].
Published: 22 March 2023
Considering elastin’s unique mechanical properties crucial for many vital functions of
human tissues and organs and its role in various biological mechanisms [4,7,8], it is not
surprising that there is a lot of interest in elastin in many research areas. Review papers on
Copyright: © 2023 by the authors.
elastin in the context of its biology and biochemistry [4,9–13], mechanical functions [1,5],
Licensee MDPI, Basel, Switzerland. diseases, and aging [14–20] are widely cited, and new data are constantly emerging. An-
This article is an open access article other important issue is the huge potential of elastin and elastin-like peptides in biomedical
distributed under the terms and applications, including advanced biomaterials and regenerative medicine [21–25].
conditions of the Creative Commons The structure of elastin and the molecular mechanism of its elasticity has been a matter
Attribution (CC BY) license (https:// of debate for several decades [26–37]. While there was a wide consensus on the entropic
creativecommons.org/licenses/by/ origin of elastin elasticity, the main difference among the models was the presence and
4.0/). nature of the ordered structures that contribute to the molecule entropy.

Biomolecules 2023, 13, 574. https://doi.org/10.3390/biom13030574 https://www.mdpi.com/journal/biomolecules

Biomolecules 2023, 13, 574 2 of 13

This work aims to provide a concise overview of the mechanical properties of elastin,
its role in tissue elasticity, and current knowledge on the molecular basis of elastin’s unique
physical performance.

2. Elasticity of Soft Tissues

The description of the mechanical behavior of tissues requires certain physical param-
eters that can be used to assess the response of tissues to applied loads. As with other
materials, the parameters that quantify the mechanical properties of the tissue are based
on the relationship between the forces acting and the result of these forces expressed in
terms of shape changes, resistance to deformation, and the energy involved in this process.
Extensibility, modulus of elasticity, elastic–strain energy, and ultimate strength can be
derived from the relationship between the force applied to the material being stretched
and the resulting extension, which is expressed in the form of stress–strain curve. The
resistance of the material against deformation when subjected to a given stress, that is,
its stiffness is expressed as Young’s modulus (modulus of elasticity) and is calculated as
the slope of the stress–strain curve within the linear region where the material deforms
fully reversibly. The higher Young’s modulus, the stiffer material and the greater its ability
to transmit forces and resist deformation [1,5,38]. Thus, a more deformable compliant
tissue will exhibit a lower elastic modulus than a less deformable “stiffer” one. As concerns
the energy absorbed by the material during deformation, elasticity implies that it will be
recovered during recoil [1,5,39]. The efficiency of energy recovery in a deformation: the
recoil cycle is expressed as resilience, which should be 100% in a fully elastic deformation.
The mechanical functionality of soft tissues is provided by fibrous components of
extracellular matrix (ECM), collagen, and elastic fibers. Collagen is the most abundant
component of the tissues ECM. It is responsible for tensile strength and plays a crucial
structural role [1,5,38,40]. A variety of collagen types give rise to an impressive diversity of
three-dimensional supramolecular structures compatible with tissues’ mechanical functions
and the forces the tissues must handle [41–43]. The main component of elastic fibers, elastin,
has a low modulus of elasticity and deforms reversibly with very high resilience. The key
function of elastin in ECM is to provide low stiffness, high extension and efficient elastic–
energy storage [1,4,5]. Although much less abundant than collagen, elastin is present
in large amounts within highly elastic tissues like arteries and lungs, where repetitive
extensions and relaxations are essential for their function [44,45]. Although mature collagen
and elastin networks function in the same tightly filled extracellular matrix, they remain
structurally independent of each other. Very few physical interactions between collagen
and elastin in the ECM have been documented [9]. However, the coexistence and synergy
of collagen and elastin networks result in the nonlinear elastic response of tissues. A typical
stress–strain curve for tissue samples is not linear but J-shaped, where initial response
at low extension is due to compliant elastin, whereas, at higher extensions, the loads are
transferred by stiffer collagen, so elastic stiffness of tissue increases with loading [1,2,38–40].
This may cause some ambiguity when attempting to quantify tissue elasticity, as the modulus
of elasticity is the function of strain.
Another cause of nonlinearity in the stress–strain relationship is the viscosity of
tissue components. Both fibrous protein networks are immersed in a water-saturated,
viscous milieu of ECM rich in glycoproteins, proteoglycans (PGs), and glycosaminoglycans
(GAGs) [3,5,46]. These viscous liquid components make the tissues not perfectly elastic.
Tissues typically exhibit viscoelastic behavior, which is due to the fact that the reaction
of fibrous components to tissue deformation in a viscous environment is time-dependent.
Moreover, the interactions between the elastic and viscous components observed in each
deformation–recoil cycle result in a dissipation of a certain amount of strain energy as heat,
and consequently, the elasticity and resilience of the tissues are never 100% [1,5,39,40].
The characteristic nonlinear nature of the stress–strain relationship with the deformation-
dependent modulus of elasticity and not perfect energy recovery is similar for different
tissues; however, their functional and ultimate strains, moduli of elasticity, and ultimate
Biomolecules 2023, 13, 574 3 of 13

strength differ greatly [21,47–51]. Table 1 presents some examples of soft tissues’ mechanical
characteristics. It should be underlined that the diversity of experimental data is affected
not only by the type of sample and its location in the tissue but also by the type and
parameters of the mechanical test performed. Moreover, determining the modulus of
elasticity in viscoelastic material may be ambiguous.

Table 1. Mechanical parameters of selected mammalian tissues.

Elastic Modulus, Maximal Strength, Maximum Strain,

Refs
(MPa) (MPa) (%)
Elastin free tendon 1200 120 13 [1]
Elastin from nuchal ligament 1.1 2 150 [1]
Arteries and veins (different species) 0.6–3.5 2 - [48]
Cortical artery (human) 21.4 4.1 145 [49]
Cortical vein (human) 3.4 1.4 193 [49]
Aortic valve leaflet human 15.6 2.6 21.9 [49]
Tendon (different spices) 43–1660 560 [48]
Tendon (human) 143–2310 24–112 - [49]
Ligament (human) 65–541 13–46 - [49]
Skin (different species) 21–39 30 [48]
Skin (rat) 25.35 7.83 46 [50]
Articular (cartilage bovine) 30 - - [51]
Auricular (cartilage bovine) 15 - - [51]

2.1. Occurrence of Elastin in Tissues

As different types of tissues exhibit different mechanical functions and requirements for
elasticity, the content and arrangement of elastin vary between and within tissues. Elastic fibers
are mostly present in elastic tissues such as the blood vessels and lungs, where their architecture
and mechanical role is well-understood and frequently described [15,18,20,39,40,44,45,52,53].
Moreover, in the skin where elastin is present in small amounts, its profound impact on
mechanical behavior has been known for many years [54]. As was discussed in detail
by Green et al. [2], elastin is a more widely distributed component of tissues than was
previously supposed, and elastin fibers approximately 1 µm in diameter are common
building blocks forming the elastic structures of many tissues. Developing microscopic
techniques have allowed the revealing of complex networks of fine elastin fibers in other
tissues such as small blood vessels, cartilage, intervertebral discs, and even in the adipose
tissue and tendons [2]. Table 2 gives an overview of elastin amounts obtained from tissues’
dry weight: from 70% in nuchal elastic ligaments to less than one percent in the meniscal
fibrous cartilage.

Table 2. Amounts of elastin in dry mass of human and bovine (*) tissues.

Elastin Amount (%) References

Nuchal ligament * ~70 [22,55]
Large arteries >50 [10]
Yellow ligament ~47 [56]
Saphenous vein ~32 [57]
Lung parenchyma 20–30, ~30 [52,58]
Auricular cartilage * 19, 20 [51,59]
Biomolecules 2023, 13, 574 4 of 13

Table 2. Cont.

Elastin Amount (%) References

Auricular cartilage 15 [60]
Heart valves 10–15 [55]
Pulmonary blood vessels 7–16 [52]
Mitral valve chordae tendineae ~5 [61]
Airways 3–5 [52]
Skin 2–4, 3–4 [10,62]
Nasal cartilage 3–5 [60]
Intervertebral disc 1.7, 2 [56,63]
Meniscus 0.6 [59]

The role of elastin in tissue elasticity results not only from its amount but also from
the spatial arrangement and the type of network being created. One of the richest sources
of elastin is the nuchal ligament, where elastin forms a filamentous network that orients
itself parallel to the direction of stretching, along the spinal cord, providing head support to
large mammals [5]. In the elastic arteries, particularly in the aortic wall where elastin is the
major component, elastin fibers surrounded by circumferentially oriented smooth muscle
cells and collagen fibers form highly organized and thick concentric lamellae. Such an
arrangement lets the artery diameter follow changes in blood pressure and hemodynamic
stresses during the cardiac cycle [20,64]. Moreover, physical connections and synergy
between elastic fibers and muscle cells ensure the proper response of the cells to mechanical
strain [65]. In the muscular arteries, where elastin fibers are also abundant, they do not
form such regular lamellar units as in elastic ones [66]. Elastin in small resistance arteries
forms a thin layer of longitudinally aligned fibers in media, while in the adventitia, the
fibers are more abundant and create a more complex network [2]. Longitudinally aligned
adventitial elastin fibers were found in arterioles subjected to longitudinal stretch [67].
Generally, the structure and the amount of elastin in different types of blood vessels
depends on their location in the circulatory system and local hemodynamic conditions. The
contribution of elastic structures to vascular biomechanics has been exhaustively studied
for decades [18,20,40,44,53,68], but new papers are constantly being published [15,65,69–75]
showing that there is still room for exploration in this area.
A complex alignment of elastin fibers can be found in the heart valves. Different
layers of the heart valve have different mechanical properties owing to the amount and
arrangement of elastin present in each layer [53]. Although they do not contribute to
stiffness and strength, the elastic fibers provide flexibility and stretch in response to the
hemodynamic environment and significantly contribute to valve performance during the
cardiac cycle [76]. A continuous mechanical efficiency of the valves is an example of perfect
mechanical cooperation between collagen and elastin within tissues ECM.
Elastin is widely distributed in the lung compartments, with the highest concentration
in the respiratory parenchyma [52]. The lung elastic fibers exhibit significant structural
heterogeneity, and the distribution of diameters and lengths of the fibers appear similar to
the distribution of collagen fibers [45].
Although present in much smaller amounts, tiny elastin fibers also have a big impact
on the properties of other tissues. The studies on the articular cartilage showed a fine
and dense network of elastin fibers located around the chondrocytes [2,77]. They seem to
protect the cells from moderate stretching forces spreading inside the loaded cartilage. At
the superficial layer, where the higher tensile strains are present, a cobweb-like elastin fiber
network is observed, which increases the resistance of the cartilage to strain in different
directions [77]. In the intervertebral disc, the multi-scale hierarchical structure of the
elastic fibers plays a significant biomechanical role [78,79]. The organization of the fibers
Biomolecules 2023, 13, 574 5 of 13

located between the lamellae of collagen fibers changes along with the load exerted on the
disc [80], age, and pathology [79,81]. In the skin, the elastic fibers form a three-dimensional
meshwork that spans from the papillary down to the deep dermis and surrounds densely
packed collagen fibers [62,82,83]. The meshwork consists of branched fibers of extremely
variable width [62]. The mechanical response of the tissue is determined by the amount
and spatial arrangement of elastin and collagen fibers relative to each other [83]. Elastic
fibers in the collateral ligament are oriented along the collagen fibers but form an isotropic
matrix in the transverse plane providing resistance to multiaxial deformations [84].

2.2. Mechanical Performance of Elastic Fiber

The ability of diverse tissues with different functional mechanical requirements to
deform and to effectively regain their shape after deformation is provided by the same
elastin-rich structure of elastic fibers [9,10]. Elastic fibers can be linearly extended more
than twice their length before rupture occurs, and once tension is released, they return to
their original dimensions without hysteresis [1].
The mammalian elastic fibers consist of an inner cross-linked and insoluble elastin
core (90% of the volume) surrounded by a shell of tiny microfibrils (10–12 nm in diam-
eter), which are two orders of magnitude smaller than the diameter of the entire elastic
fiber [5,14,85]. The complex process of elastic fiber formation is regulated at multiple steps,
including coacervation, deposition, cross-linking, and assembly of insoluble elastin onto
indispensable microfibril scaffolds [4,5,8,9,13,14,86,87]. Fibrillin is the major component of
microfibrils. There are species- and tissue-dependent differences in the expression levels
of three isotypes of fibrillin, with fibrillin-1 being the predominant isotype found in adult
human tissues [9,88–90]. Although fibrillin is the major component of the microfibrils, an
array of other less abundant molecules is necessary, including latent transforming growth
factor-β binding proteins (LTBPs), matrix-associated glycoproteins (MAGPs), members of
the fibulin family, and PGs. They play an essential role in the organization of fibers, but
also their complex hierarchical assembly supports the biological functions of microfibrils,
including induction of cellular responses to mechanical forces derived from the matrix
microenvironment [10,14,87,91]. Therefore, the two basic components of an elastic fiber
have distinct tasks in the tissue ECM; elastin stores energy of deformation and provides
passive recoil, whilst fibrillin microfibrils direct elastogenesis, mediate cell signaling, and
maintain tissue homeostasis [9,11,14,89,90].
Young’s modulus of elastic fiber-rich samples from purified arteries ranged at 0.13–0.65 MPa
in dog and sheep aorta [92] and between 0.1 and 0.8 MPa in pig aorta [93]. Young’s modulus
of single elastic fibers isolated from bovine nuchal ligament ranged at 0.4–1.2 MPa [26].
According to Koenders et al. report [85], it was within the range of 0.3–1.5 MPa.
So, the stiffness of elastin expressed in terms of Young’s modulus is at least two orders
of magnitude smaller than that of collagen [1,39]. In general, low Young’s modulus is due
to the high extensibility of the material, and in fact, the maximum elastic elongation of
elastin exceeds 100% [1]. The breaking strain was reported to be up to 200% [26].
Another interesting issue is whether the mechanical properties of tissues result from
elastin molecules or do fibrillin–microfibrils play a role. The contribution of microfibrils to
the mechanical performance of the meshwork of elastic tissue was experimentally studied
in pig aorta [93] and in bovine nuchal ligament [85]. Removal of the microfibrils from
elastic fibers from the pig aorta reduced the modulus at low strains by a few percent and
increased the modulus at high strains, suggesting that the microfibrils have the capacity
to change the orientation of elastin fibers, possibly transmitting some of the load from
one elastin fiber to another [93]. Koenders et al. [85] showed that Young’s moduli of
single elastic fibers from bovine nuchal ligament were not significantly affected by the
absence or presence of fibrillin–microfibrils. Young’s modulus for pure fibrillin–microfibrils
ranged from 0.56–0.74 MPa, which was comparable with Young’s modulus of elastic fibers
cited above. They concluded that fibrillin–microfibrils did not significantly influence the
mechanical properties of single elastic fibers in the vertebrate. However, Sherratt et al. [94],
Biomolecules 2023, 13, 574 6 of 13

based on the linear springs model of microfibrils, estimated Young’s modulus of single
fibrillin–microfibrils from zonular filaments of the eye to be 78–96 MPa, which was two
orders of magnitude higher than the modulus determined for elastic tissue samples. The
authors suggested that microfibrils have their own mechanical role in elastic fibers and act
as relatively stiff reinforcing components in a fibrous composite. Megill et al. [95] showed
that reinterpretation of the data presented by Sherratt et al. [94] in terms of the nonlinear
model of mechanical behavior should result in at least one order of magnitude lower value.
They suggested Young’s modulus of 1 MPa for fibrillin–microfibrils in a fiber-reinforced
composite model.

2.3. Driving Force of Elastic Recoil

To understand the origin of the mechanical efficiency of tissues both in a healthy
and diseased or/and aging organism, we must remember that the basis for elasticity and
resilience of tissues is an exceptional capability of cross-linked elastin fibers to extreme
deformation under small loads and next spontaneous recoil back to the original shape with
minimal energy loss. In all materials, also in living tissues, elastic recoil after deformation
results from the sum of two different physical driving forces. One of them appears as a
reaction to internal energy changes when the applied deforming force distorts the molecular
structure of the material and results from the tendency of each molecular system to a
spontaneous regain of the state of the lowest potential energy. The other one results from
a thermodynamic principle stating that isolated systems spontaneously arrive at a state
where entropy is the highest in given circumstances. The first process dominates in stiff
materials with ordered molecular structure, while the other one is in elastomers, elastically
deformable polymers characterized by a high degree of conformational disorder which
makes the elastomers in a relaxed state have high entropy [6,96]. There are two essential
molecular attributes of material with entropic elasticity: flexible polymer chains and the
presence of cross-links between them. Elastin structure is characterized by a high degree of
conformational disorder, which makes it flexible and easily stretched, and by a high degree
of cross-linking, resulting in a network capable of distributing the deformation-related
stresses and strains throughout the polymer. The entropic component of elastin elasticity
is more than 70% [96]. Thus a passive, entropy-driven mechanism allowing the recoil of
elastic fibers after stretching endows the extracellular matrix of connective tissues with
their elasticity and resilience.
Various models of entropic elasticity have been proposed, ranging from maximally
disordered isotropic structure [28,29] to highly organized arrays of beta-spirals and beta-
turns [33], and the main driving force of elastic recoil has been sought either in the confor-
mational entropy of polypeptide chains [29] or in the entropy of librational motions of fixed
secondary structures suspended between mobile chain segments [33] or in the hydrophobic
effect [28,30]. The current consensus is based on a model in which the water-swollen hy-
drophobic domains of elastin molecules form highly disordered but not a random assembly
of dynamic conformations devoid of permanent secondary structures [31,32,35–37].

2.4. Molecular Basis of Elastin Elasticity

In all tissues, no matter how different they are, the basis of elasticity is the same
and is “encoded” in the molecular structure of elastin. Human elastin is secreted prin-
cipally from fibroblasts and smooth muscle cells as tropoelastin, a highly hydrophobic,
~60 kDa unglycosylated monomer. The primary sequence of tropoelastin is formed by an
arrangement of two major types of alternating domains, the hydrophobic domains and
the hydrophilic lysine-rich domains [97–99]. The hydrophobic domains are rich in glycine,
proline, and valine, commonly arranged in combinations of GV, GVA, and PGV sequences.
The hydrophilic helical domains of tropoelastin contain lysine residues spaced three or four
residues apart and typically flanked by alanines. In the extracellular space, the tropoelastin
units are chaperoned to the cell surface, where they coacervate into protein-rich spherules
and then undergo cross-linking and fibril assembly onto microfibril scaffolds, which has
Biomolecules 2023, 13, 574 7 of 13

been described many times and is updated every few years [8,10,13,86,87,99–103]. The cross-
linking of tropoelastin monomers occurs via lysine residues present in helical domains
through the action of lysyl oxidases, which results in the formation of tetra-functional
desmosine and isodesmosine linkages and bi-functional allysine–aldol and lysinonor-
leucines. Cross-linking between hydrophilic helical domains of elastin monomers stabilizes
elastin microfibrils and provides elastic fibers with structural integrity and durability, and
contributes to their high insolubility. Recent reviews of elastin cross-links biochemistry are
available in refs. [8,87,104,105].
While elastin’s high structural integrity and durability are due to cross-links formed
in its hydrophilic domains, its elasticity results from the specific sequences of hydropho-
bic amino acids. However, despite the strong hydrophobicity of the elastin monomer
containing ~80% non-polar amino acids in its structure, hydration of elastin is an abso-
lute requirement for elasticity [1,30,37,97]. Dry elastin is hard and brittle, while elastin
monomers in a water environment are disordered and flexible [31,37]. They retain backbone
mobility even after aggregation [31] and in mature cross-linked fibers [36].
In general, proteins composed of non-polar amino acids tend to form tightly packed
and ordered secondary structures shielding non-polar side chains from the surrounding po-
lar environment. In the elastin monomer surrounded by water, the formation of an ordered
secondary structure is prevented by high glycine and proline content, which accounts for
30% and 12% of its amino acids, respectively [31]. The fixed φ dihedral angle and lack of
amide hydrogen of proline, as well as the flexibility of small glycine, make their sequences
prevent the formation of a compact, water-excluding core, which maintains a high degree of
structural disorder and allows water molecules to spread among elastin network [31]. The
solvent water molecules act on elastin as a plasticizer by interacting with water bound to the
main chain, which allows the chain to be more mobile [30]. Although the sequences of hy-
drophobic amino acids prevent the formation of large secondary structures, the dynamics of
the hydrated backbone of the elastin molecule results in transient hydrogen-bonded turns,
which form highly disordered, but not random, assemblies of dynamic conformations such
as short and labile beta structures and polyproline II helices [31,37]. Both molecular dynam-
ics simulations of elastin-like peptides sequences [30,32] and solid-state NMR experiments
with mature elastin [36,106] reveal the extremely dynamic nature of hydrophobic domains
providing high entropy of elastin in the relaxed state (Figure 1, left side). Rausches and
Pomes [32], based on massive-scale molecular dynamics simulations, describe the assembly
of elastin individual chains in water as a maximally disordered, melt-like state—a liquid
state of elastin. However, it has been shown that also hydrophilic, alanine-rich cross-linking
domains can significantly contribute to complex elastin conformations [107].
The extension of cross-linked elastin leads to a decrease in the conformational entropy
of individual chains as well as polymerized material (Figure 1, right side). Thus, both the
hydrophobic effect and conformational entropy related to a high structural disorder of the
polypeptide chain drives the elastic recoil of stretched elastin molecules. However, there
is still a lack of full understanding of all the mechanisms underlying the extraordinary
elasticity of cross-linked elastin in elastic fibers.

2.5. Degradation of the Elastic Fiber Mechanical Performance

Elastin expression in mammals begins in mid-gestation and continues at high levels
through childhood. However, elastin synthesis after adolescence is diminished; thus, ma-
ture elastic fibers have to fulfill their biomechanical function almost over the entire life of
the organism. In contrast to continuously synthesized intracellular proteins, elastic fiber
proteins are remarkably long-lived, with an in vivo half-life of elastin in humans estimated
to be of 70 years [9,14,108]. The composition of elastin molecules, extremely dense packing,
and high degree of crosslinking make elastin the most stable of the extracellular matrix
molecules [1,4,9,11]. Consequently, elastic fibers are resistant to most influences and, under
normal conditions, are able to undergo billions of cycles of extension and recoil without
mechanical failure. However, it is commonly observed that in aging humans, cardiovascu-
Biomolecules 2023, 13, 574 8 of 13

lar, pulmonary, and dermal tissues become increasingly stiff and lose their essential ability
to regain shape in a fast and effective way. The loss of elasticity in the skin, blood vessels,
lungs, and other tissues is an undoubted sign of the aging process. The loss of functionality
of elastic fibers is due to both fragmentation and/or thinning of elastin networks as well as
modifications of the elastic properties of the fibers themselves [16,17,19,72,108,109]. The
Biomolecules 2023, 13, x FOR PEER REVIEW 8 of 13
effect of fibers degeneration results in an excessive transfer of mechanical loads to collagen
and the consequent stiffening of tissues [1,5,20].

Figure1.1.Simplified
Figure Simplifiedmodel
modelofofhydrated
hydrated crosslinked
crosslinkedelastin; helical,
elastin; hydrophilic
helical, hydrophilicdomains
domainsof polypep-
of poly-
peptide
tide chainschains (magenta),
(magenta), cross-linking
cross-linking betweenbetween
helicalhelical
domains domains
(green),(green), hydrophobic
hydrophobic domainsdomains
(red),
(red), peptide–peptide
peptide–peptide hydrogenhydrogen bonds (black),
bonds (black), solvating
solvating water Folded,
water (blue). (blue). Folded, native
native state state
(left (left
side)—
side)—Prolines
Prolines and glycines
and glycines preventprevent the hydrophobic
the hydrophobic collapsecollapse of the hydrophobic
of the hydrophobic domains, domains, which
which allows
allows water molecules to spread among the elastin network; interactions of the solvent water
water molecules to spread among the elastin network; interactions of the solvent water molecules
molecules with water bound to the main chain allow for the chain mobility and result in transient
with water bound to the main chain allow for the chain mobility and result in transient hydrogen-
hydrogen-bonded turns as short and labile folded structures. Extended state (right
bonded turns as short
side)—Extension and labile
of elastin leadsfolded structures.
to a decrease Extended stateentropy
of conformational (right side)—Extension
of the polypeptideof elastin
chains
leads to a decrease of conformational entropy of the polypeptide chains and increases
and increases hydrophobic interactions with exposed hydrophobic residues; both the hydrophobic hydrophobic
interactions with exposed entropy
effect and conformational hydrophobic
of theresidues; both
chain drive thethe hydrophobic
elastic effect andelastin
recoil of stretched conformational
molecules.
entropy of the chain drive the elastic recoil of stretched elastin molecules.
The extension of cross-linked elastin leads to a decrease in the conformational en-
tropyTheof progressive
individual chainsloss ofasthe mechanical
well function
as polymerized of aging
material fibers
(Figure 1, isright
a consequence
side). Thus,
of a continuous accumulation of damage resulting from
both the hydrophobic effect and conformational entropy related to a high structuralchemical and physical pro- dis-
cesses induced by both intrinsic and extrinsic factors. Based on
order of the polypeptide chain drives the elastic recoil of stretched elastin molecules. the current models and
reviews
However, [8,14,16,17,19,110],
there is still a lackthe of mechanisms of elastic
full understanding fibers
of all degradation underlying
the mechanisms can be briefly the
summarized as follows. The very low turnover of
extraordinary elasticity of cross-linked elastin in elastic fibers.the fibers makes them prone to enzy-
matic proteolysis by the family of extracellularly acting proteinases, as well as to reactive
oxygen species (ROS)-mediated
2.5. Degradation of the Elastic Fiber oxidation,
Mechanical formation of advanced glycation end-products
Performance
(glucose-mediated cross-linking), calcium accumulation, binding of lipids and lipid perox-
idationElastin expression
products, in mammals
carbamylation, begins in mid-gestation
time-dependent modification andofcontinues
aspartic acid at high levels
residues,
through childhood. However, elastin synthesis after adolescence
and mechanical fatigue. Moreover, extensive research has shown that calcification, choles- is diminished; thus,
mature elastic fibers have to fulfill their biomechanical function almost
terol binding, glycation, enzymatic degradation resulting in the release of elastokines, and over the entire life
of the organism.
chronic low-gradeIninflammation
contrast to continuously
can complement synthesized
and enhance intracellular proteins,
each other. It waselastic
shown fi-
ber proteins are remarkably long-lived, with an in vivo half-life
that even though a healthy lifestyle can help reduce extrinsic risk factors and is able toof elastin in humans es-
timated to
postpone thebe of 70
onset years [9,14,108].
of elastic The composition
fibers weakening, it cannot fully of prevent
elastin molecules, extremely
intrinsic degradation
dense packing, and high degree of crosslinking make elastin the
processes in the extracellular matrix of aging tissues. Robert et al. [111] have estimated most stable of thethatex-
tracellular
an upper limit matrix molecules
for the mechanical[1,4,9,11]. Consequently,
performance elastic cardiorespiratory
of the human fibers are resistant to most
system is
influences
about 100–120 and,years.
underHowever,
normal conditions,
intensificationare able
and/orto undergo
coexistence billions of cycles ofmecha-
of degradative exten-
sion and
nisms can recoil
cause without mechanicalinvolving
severe pathologies failure. However, it is commonly
the cardiovascular system,observed
skin andthatlungs in
aging humans, cardiovascular, pulmonary,
much earlier, not only at an advanced age [8,14,19,110]. and dermal tissues become increasingly stiff
and Though
lose their theessential
gradualability to regain
degradation shape fiber
of elastic in a and
fast associated
and effective way. The loss
dysfunctions result of
elasticity in
inevitably the multiple
from skin, blood vessels, lungs,
physiological and other
intrinsic tissues
processes and is some
an undoubted sign of im-
extrinsic factors the
aging process.
pairing The loss of afunctionality
tissue homeostasis, certain number of elastic fibers elastic-fiber
of inherited is due to both fragmentation
pathologies were
and/or
also thinningThey
recognized. of elastin
resultnetworks as wellinas
from mutations themodifications
genes encoding of the elastic
elastin, properties
fibrillin, and/or of
the fibers themselves [16,17,19,72,108,109]. The effect of fibers degeneration results in an
excessive transfer of mechanical loads to collagen and the consequent stiffening of tissues
[1,5,20].
The progressive loss of the mechanical function of aging fibers is a consequence of a
continuous accumulation of damage resulting from chemical and physical processes in-
Biomolecules 2023, 13, 574 9 of 13

other proteins involved in microfibril and elastic fiber assembly. Marfan syndrome is the
most frequent genetic disease directly associated with mutations in the fibrillin genes [14].
A detailed list and description of mutations and symptoms in inherited elastin- and elastic-
fibers pathologies can be found in a detailed review by Baldwin et al. [14] and more recent
ones [110,112].

3. Conclusions
The aim of this paper was to overview the literature regarding the role of elastin in
the elasticity and mechanical performance of tissues as well as a brief description of the
molecular model of elastin’s unique properties.
Elastin is a unique long-living molecule that works as strain–energy storage and
provides vertebrate tissues with the extensibility and elasticity necessary for the functioning
of vital organs. Different mechanical requirements of various tissues are met by the same
elastin-rich structure, i.e., elastic fiber. The variety of mechanical functions and resulting
mechanical parameters of tissues are provided by different amounts of elastic fibers, their
arrangement, and mechanical cooperation with other components of the tissue extracellular
matrix. Moreover, the analysis of experimental data referring to tissues should also account
for other factors, such as the nonlinear strain–stress relationship in viscoelastic materials
and testing methods.
There is a consensus on the entropic origin of elastin elasticity; however, the nature
of the structures that contribute to the molecule entropy is continually being studied. In
the currently accepted model, high proline and glycine content in the elastin monomer
prevents the formation of compact hydrophobic structures and allows water to spread
among elastin molecules. The water-swollen hydrophobic elastin domains form a highly
disordered and dynamic, but not random, assembly of conformations devoid of permanent
secondary structures.
Numerous significant advances in life sciences produced evidence that elastic fibers
and their breakdown products, especially elastokines, are implicated in the etiology of
numerous diseases as well as in aging-related health problems. Even though modern
experimental and simulation methods brought a huge insight into the biology and physical
interactions of elastin, some aspects of its functioning in the ECM structures, as well as
mechanisms of the enormous flexibility of cross-linked elastin, remain unexplained. Further
expansion of knowledge of their synthesis and decomposition would aid the development
of innovative treatment methods and should hopefully lead to new strategies for elastic
fiber repair and regeneration.

Author Contributions: Conceptualization, H.T.; methodology, A.B. and H.T.; formal analysis, H.T.;
data curation, A.B. and H.T.; writing—original draft preparation, A.B. and H.T.; writing—review and
editing, H.T. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

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