Ambient atmospheric aerosol particles comprised of various inorganic and organic substances ubiqu... more Ambient atmospheric aerosol particles comprised of various inorganic and organic substances ubiquitously undergo phase transition, such as efflorescence, amorphization, and especially liquid-liquid phase separation (LLPS). Resultant changes of physicochemical properties in aerosols then deeply affect the climate system. However, finely detecting these processes occurring in single aerosol particles, especially under the acidic condition of real atmospheric environment, remains a challenge. In this work, we investigated the pH-dependent phase separation in single levitated microdroplets using a self-developed laser tweezers Raman spectroscopy (LTRS) system. The dynamic process of LLPS in laser-trapped droplets over the course of humidity cycles was detected with the time-resolved cavity-enhanced Raman spectra. These measurements provide the first comprehensive account of the pH-dependent LLPS in single levitated aerosol microdroplets and bring possible implications on phase separation in actual atmospheric particles.
Accurate calibrations of stiffness and position are crucial to the quantitative measurement with ... more Accurate calibrations of stiffness and position are crucial to the quantitative measurement with optical tweezers. In this paper, we present a new calibration scheme for optical tweezers including stiffness and position calibrations. In our system, acousto-optic deflectors (AODs) are used as laser beam manipulating component. The AODs are controlled by a field programmable gate array (FPGA) connected to a computer using universal serial bus (USB) communication mode. Our results agree well with the present theory and other experimental results. OCIS codes: 120.0120, 170.0170.
We carry out in situ single-molecule measurements of the specific interaction between apolipoprot... more We carry out in situ single-molecule measurements of the specific interaction between apolipoprotein A-I (apoA-I) and ATP binding cassette transporter A1 (ABCA1) on THP-1 cells. Single-molecule force spectroscopy shows that similar to normal apoA-I, the dysfunctional apoA-I from diabetes patients interacts with ABCA1 via two different binding sites on the cells. The strength of dysfunctional apoA-I binding to a high-capacity binding site is 26.5±4.9 pN. The minor direct apoA-I/ABCA1 binding strength is 56.7±4.1 pN. These results facilitate a pathological understanding of the mechanisms that underlie the specific interaction of apoA-I and ABCA1 at the single-molecule level.
We investigate the activation of living monocytic U937 cells induced by interleukin-6 (IL-6) at t... more We investigate the activation of living monocytic U937 cells induced by interleukin-6 (IL-6) at the single cell level. We employ home-built Raman tweezers to measure the Raman spectra of living U937 cells with and without IL-6 at the single cell level. Raman peaks of amide III, amide I, DNA backbone, as well as guanine and adenine in U937 cells, change at 1312, 1652, 1090, and 1576 cm −1 , respectively, shortly after IL-6 is added in the medium. The change is a dynamic temporal process. In the activation process of U937 cells induced by IL-6, the protein signals recover in 20 min, while the nucleic acid signals continue to increase for 20 min. The results reveal that the biochemical cascades of activation in signal transduction induced by IL-6 can be investigated in situ at the single cell level.
Laser tweezers can capture and move small particles. It has advantages such as non-contact and no... more Laser tweezers can capture and move small particles. It has advantages such as non-contact and non-invasive, which make it very useful in biology, medicine, materials fields. Laser scissors or laser micro-beam can perforate or cut biological tissue with sub-micron accuracy. A workstation combining the two technologies together acting as a cellular operating lab is introduced in this paper. Our system features a multifunctional and user-friendly control software, which make the system effective and convenient. Based on this control program both laser tweezers and scissors can be operated with a computer automatically. In addition, some self-developed devices such as PZT drivers and photodetector give the system a high performance in accuracy and stability. All these make our system convenient, multifunctional and powerful.
The magic wavelength is a crucial parameter for the optical frequency standard field. In this pap... more The magic wavelength is a crucial parameter for the optical frequency standard field. In this paper, we have calculated the dipole polarizabilities of the ground state ns2 \rm ^{1}S_{0} and the metastable state nsnp \rm ^{3}P_{0} for strontium and ytterbium by the method of the B-spline configuration interaction with a semiempirical core-polarization model potential, and finally obtained the values of
Correction for 'Fast label-free recognition of NRBCs by deep-learning visual object detection and... more Correction for 'Fast label-free recognition of NRBCs by deep-learning visual object detection and singlecell Raman spectroscopy' by Teng Fang et al., Analyst, 2022,
A computer-assisted and label-free method to quickly recognize the rare nucleated red blood cells... more A computer-assisted and label-free method to quickly recognize the rare nucleated red blood cells by combining visual object detection with single-cell Raman spectroscopy.
In this paper, we realize dynamic holographic optical tweezers (HOT) using a commercial twisted-n... more In this paper, we realize dynamic holographic optical tweezers (HOT) using a commercial twisted-nematic liquid crystal display (TN-LCD) removed from a video projector, and manipulate multiple particles simultaneously. After measuring the parameters of the TN-LCD, we find that it is not suited to work as a phase-only modulator for infrared optical tweezers because of the small range of its phase modulation. To overcome this shortcoming, we employ binary computer-generated holograms obtained with the Gerchberg-Saxton algorithm instead of kinoforms, and optimize the diffraction efficiency of the TN-LCD by the choice of the polarization angel of the input laser and the two grey level video signals driving the TN-LCD. Since TN-LCDs are more prevalent than other types of LC devices, such as parallel-aligned nematic and ferroelectric LC devices, our approach provides an easier and lower-cost access to the set-up of a HOT system.
Raman optical tweezers (ROT) as a label-free technique plays an important role in single-cell stu... more Raman optical tweezers (ROT) as a label-free technique plays an important role in single-cell study such as heterogeneity of tumor and microbial cells. Herein, we designed a chip combining ROT to isolate a specific single cell. The chip was made from a polydimethylsiloxane (PDMS) slab which shaped a gourd-like reservoir with a connected channel on a cover glass. On the chip an individual cell could be isolated away from a cell crowd, then extracted out along with ~0.5μL phosphate buffered saline (PBS) via a pipette immediately after Raman spectral measurements of the same cell. As verification testing, we separated four different type of cells including BGC823 gastric cancer cells, erythrocytes, lymphocytes and E. coli cells, and quantifiably characterized the heterogeneity of the cancer cells, leukocyte subtype, and erythrocyte status, respectively. The average time of identifying and isolating a specific cell was 3 minutes. Cell morphology comparison and viability tests shown the successful rate of single-cell isolation was about 90%. Thus we believe our platform could further couple other single-cell techniques such as singlecell sequencing and become a multi-perspective analytical approach at the level of a single cell.
The dipole polarizabilities of the ground state ns 2 1 S 0 and the metastable state nsnp 3 P 0 ar... more The dipole polarizabilities of the ground state ns 2 1 S 0 and the metastable state nsnp 3 P 0 are crucial for estimating the light shifts and blackbody radiation shifts in the optical frequency standard based on alkalineearth-metal-like atoms. In this paper, the correlative dipole polarizabilities for group IIB atoms were calculated by the method of the B-spline configuration interaction with a semiempirical core-polarization model potential. The results are consistent with the experimental values in a reasonable accuracy and agree with other theoretical results as well. With these results, the magic wavelengths, at which the lowest-order light shift of the clock transition ns 2 1 S 0-nsnp 3 P 0 is null, were also obtained. For Zn, Cd, and Hg, they are 413, 420, and 363 nm, respectively.
Abstract Microsphere-assisted super-resolution imaging (MSI) is a label-free and wide-field imagi... more Abstract Microsphere-assisted super-resolution imaging (MSI) is a label-free and wide-field imaging technique, which draws much attention in the field. Here, a novel characteristic of MSI was reported. We demonstrated microsphere-assisted microscope possesses certain tomographic ability in the imaging of multilayer structure sample, Blu-ray disc (BD), resolving both periodic stripes and sub-surface recording marks which locate at different lays on BD, and performs the best vertical resolving under a short-wavelength illumination. Moreover, the magnification generated by microsphere and the lateral resolution in MSI, as well as their relationship, were discussed. Furthermore, our experiments show that a higher relative refractive index between the microsphere and immersion medium brings greater magnification, rather than better resolution, and theoretical simulation suggests that narrower beam waist focused by microsphere leads to better resolution in MSI.
Frequency is the most accuracy measurement quantity in the nature.Frequency Standards is the stan... more Frequency is the most accuracy measurement quantity in the nature.Frequency Standards is the standard of frequency measurement,it based on atomic transfer spectra lines which is high accuracy and stability.In the study of frequency standards there are almost problems of atomic physics,such as atomic structure and spectroscopy,interaction between atom and electronic and magnetic fields,and atom collision processes.In this paper the basic principle and application of frequency standards was given,and the atomic physical problem relative to frequency standards was briefly reviewed.
Drug resistance and heterogeneous characteristics of human gastric carcinoma cells (BGC823) under... more Drug resistance and heterogeneous characteristics of human gastric carcinoma cells (BGC823) under the treatment of paclitaxel (PTX) were investigated using single-cell Raman spectroscopy (RS). RS of normal and drug-resistant BGC823 cells (DR-BGC823) were collected and analyzed using arithmetic, statistic and individual spectrum analysis. The dynamic effects of paclitaxel (PTX) in normal and DR-BGC823 cells were evaluated dynamically. The RS intensity changed with PTX over time and produced distinct different results for the two types of cells. The average RS intensities of the normal BGC823 cells initially decreased and then increased under PTX treatment after 24 hours. In contrast, upon exposure to PTX, the average intensity of the DR-BGC823 cells initially increased within 12 hours and then gradually decreased and approached a steady state. The temporal variation of the typical component in the cells was analyzed by comparing the ratios between Raman bands. More importantly, the heterogeneous characteristics of the BGC823 cells under PTX treatment were quantified and clustered using hierarchical trees combined with RS intensity changes. The 'outlier' cells related to drug resistance were discriminated. The heterogeneity of the normal BGC823 cells under drug treatment gradually appeared over time, and was evaluated with the eigenvalues of principal component analysis (PCA). Our study indicates that single-cell RS may be useful in systematically and dynamically characterizing the drug response of cancer cells at the single-cell level.
Editorial on the Research Topic Quantum precision measurement and cold atom physics Ever since th... more Editorial on the Research Topic Quantum precision measurement and cold atom physics Ever since the invention of the cesium beam atomic clock in 1955, quantum frequency standards have seen considerable development over the decades, as a representative of quantum precision measurement. The progress in frequency measurements achieved in the past allows one to perform measurements of other physical and technical quantities with unprecedented precision, whenever they could be traced back to frequency measurements. Using atomic transitions as frequency references, quantum frequency standards are far less susceptible to external perturbations, and the quantum identity principle of microscopic particles allows easy replication of quantum frequency standards with the same frequency at any time and place. With laser cooling and trapping, cold atomic ensembles eliminate Doppler shift broadening and have become the go-to quantum reference when precision is required. The advancement of laser cooling and cold atom physics, in addition to novel physical matter states such as Bose-Einstein Condensation, gives rise to new experimental techniques in quantum precision measurement, especially quantum frequency standards, such as cesium fountain clocks dictating the SI second, as well as optical lattice clocks and single-ion optical clocks pushing the Frontier of Quantum Metrology. Other areas of quantum metrology, such as gravitometers and magnetometers, also benefit greatly from cold atoms. Challenges still remain, as researchers strive to push forward the limit in quantum precision measurement and search for novel physical phenomena in cold atomic systems. In this regard, we organized the Research Topic "Quantum Precision Measurement and Cold Atom Physics" in Frontiers in Physics. As a tribute to his 90th birthday on September 20, we dedicate this Research Topic to the venerable Prof. Yiqiu Wang, a pioneering figure in China's development of quantum precision measurement and cold atom physics. Chen et al. chronicled the scientific career
Intermolecular interactions dominate the behavior of signal transduction in various physiological... more Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (≈35 pN and ≈90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in ≈10−30 pN alterations in Ras-BRaf intermolecular binding force. The magnitude of changes in Ras-BRaf binding force correlates with the size of alterations in protein affinity and in α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptor (-R)-mediated synaptic transmission in neurons expressing replacement BRaf mutants, and predicts the extent of learning impairments in animals expressing replacement BRaf mutants. These results establish single-molecule force spectroscopy as an effective platform for evaluating the piconewton-level interaction of signaling molecules and predicting the behavior outcome of signal transduction. Intermolecular interactions hold the key to understanding of the behavior of signal transduction mediating various physiological and pathological cell processes, yet precisely assessing the interactions of signaling effectors remains a daunting task. [1,2] Biochemical assays are the frequently used to evaluate the interactions since it directly measures the binding affinity of signaling effectors, although the approach often requires bulk samples and has limited resolution. [3-7] Recently, the evolution-and/or structure-based computational modeling has emerged as an alternative approach to estimate protein-protein interactions, but the calculation may not always achieve the desired accuracy, and can be sometimes challenging. [2,8,9] Single-molecule force spectroscopy, such as optical and magnetic tweezers, have been used as a powerful toolbox to investigate the forces and motions associated with cytoskeletal motors, ligand-receptor pairs, DNAs, RNAs, and viruses. [10-14] However, whether this piconewton resolution approach may be adapted for dissecting inter-molecular interactions and interrogating signal transduction behavior is still unclear. Rapid advances in genetic and genomics-sequencing techniques have identified nearly complete lists of genes and gene products involved in the major signaling networks in living organisms and associated large numbers of mutations on the genes with many human diseases. [15-20] However, these gene products and mutations alone reveal relatively little about regulation of signaling networks and pathogenesis of human diseases. For example, an extensive amount of early work has led to the definition of several key signaling components in the canonical MAPK pathway that mediates growth, proliferation, differentiation, oncogenesis, cognition, and mental illness. [2,17,18] In neuronal cells, this MAPK pathway Lim et al.
Ambient atmospheric aerosol particles comprised of various inorganic and organic substances ubiqu... more Ambient atmospheric aerosol particles comprised of various inorganic and organic substances ubiquitously undergo phase transition, such as efflorescence, amorphization, and especially liquid-liquid phase separation (LLPS). Resultant changes of physicochemical properties in aerosols then deeply affect the climate system. However, finely detecting these processes occurring in single aerosol particles, especially under the acidic condition of real atmospheric environment, remains a challenge. In this work, we investigated the pH-dependent phase separation in single levitated microdroplets using a self-developed laser tweezers Raman spectroscopy (LTRS) system. The dynamic process of LLPS in laser-trapped droplets over the course of humidity cycles was detected with the time-resolved cavity-enhanced Raman spectra. These measurements provide the first comprehensive account of the pH-dependent LLPS in single levitated aerosol microdroplets and bring possible implications on phase separation in actual atmospheric particles.
Accurate calibrations of stiffness and position are crucial to the quantitative measurement with ... more Accurate calibrations of stiffness and position are crucial to the quantitative measurement with optical tweezers. In this paper, we present a new calibration scheme for optical tweezers including stiffness and position calibrations. In our system, acousto-optic deflectors (AODs) are used as laser beam manipulating component. The AODs are controlled by a field programmable gate array (FPGA) connected to a computer using universal serial bus (USB) communication mode. Our results agree well with the present theory and other experimental results. OCIS codes: 120.0120, 170.0170.
We carry out in situ single-molecule measurements of the specific interaction between apolipoprot... more We carry out in situ single-molecule measurements of the specific interaction between apolipoprotein A-I (apoA-I) and ATP binding cassette transporter A1 (ABCA1) on THP-1 cells. Single-molecule force spectroscopy shows that similar to normal apoA-I, the dysfunctional apoA-I from diabetes patients interacts with ABCA1 via two different binding sites on the cells. The strength of dysfunctional apoA-I binding to a high-capacity binding site is 26.5±4.9 pN. The minor direct apoA-I/ABCA1 binding strength is 56.7±4.1 pN. These results facilitate a pathological understanding of the mechanisms that underlie the specific interaction of apoA-I and ABCA1 at the single-molecule level.
We investigate the activation of living monocytic U937 cells induced by interleukin-6 (IL-6) at t... more We investigate the activation of living monocytic U937 cells induced by interleukin-6 (IL-6) at the single cell level. We employ home-built Raman tweezers to measure the Raman spectra of living U937 cells with and without IL-6 at the single cell level. Raman peaks of amide III, amide I, DNA backbone, as well as guanine and adenine in U937 cells, change at 1312, 1652, 1090, and 1576 cm −1 , respectively, shortly after IL-6 is added in the medium. The change is a dynamic temporal process. In the activation process of U937 cells induced by IL-6, the protein signals recover in 20 min, while the nucleic acid signals continue to increase for 20 min. The results reveal that the biochemical cascades of activation in signal transduction induced by IL-6 can be investigated in situ at the single cell level.
Laser tweezers can capture and move small particles. It has advantages such as non-contact and no... more Laser tweezers can capture and move small particles. It has advantages such as non-contact and non-invasive, which make it very useful in biology, medicine, materials fields. Laser scissors or laser micro-beam can perforate or cut biological tissue with sub-micron accuracy. A workstation combining the two technologies together acting as a cellular operating lab is introduced in this paper. Our system features a multifunctional and user-friendly control software, which make the system effective and convenient. Based on this control program both laser tweezers and scissors can be operated with a computer automatically. In addition, some self-developed devices such as PZT drivers and photodetector give the system a high performance in accuracy and stability. All these make our system convenient, multifunctional and powerful.
The magic wavelength is a crucial parameter for the optical frequency standard field. In this pap... more The magic wavelength is a crucial parameter for the optical frequency standard field. In this paper, we have calculated the dipole polarizabilities of the ground state ns2 \rm ^{1}S_{0} and the metastable state nsnp \rm ^{3}P_{0} for strontium and ytterbium by the method of the B-spline configuration interaction with a semiempirical core-polarization model potential, and finally obtained the values of
Correction for 'Fast label-free recognition of NRBCs by deep-learning visual object detection and... more Correction for 'Fast label-free recognition of NRBCs by deep-learning visual object detection and singlecell Raman spectroscopy' by Teng Fang et al., Analyst, 2022,
A computer-assisted and label-free method to quickly recognize the rare nucleated red blood cells... more A computer-assisted and label-free method to quickly recognize the rare nucleated red blood cells by combining visual object detection with single-cell Raman spectroscopy.
In this paper, we realize dynamic holographic optical tweezers (HOT) using a commercial twisted-n... more In this paper, we realize dynamic holographic optical tweezers (HOT) using a commercial twisted-nematic liquid crystal display (TN-LCD) removed from a video projector, and manipulate multiple particles simultaneously. After measuring the parameters of the TN-LCD, we find that it is not suited to work as a phase-only modulator for infrared optical tweezers because of the small range of its phase modulation. To overcome this shortcoming, we employ binary computer-generated holograms obtained with the Gerchberg-Saxton algorithm instead of kinoforms, and optimize the diffraction efficiency of the TN-LCD by the choice of the polarization angel of the input laser and the two grey level video signals driving the TN-LCD. Since TN-LCDs are more prevalent than other types of LC devices, such as parallel-aligned nematic and ferroelectric LC devices, our approach provides an easier and lower-cost access to the set-up of a HOT system.
Raman optical tweezers (ROT) as a label-free technique plays an important role in single-cell stu... more Raman optical tweezers (ROT) as a label-free technique plays an important role in single-cell study such as heterogeneity of tumor and microbial cells. Herein, we designed a chip combining ROT to isolate a specific single cell. The chip was made from a polydimethylsiloxane (PDMS) slab which shaped a gourd-like reservoir with a connected channel on a cover glass. On the chip an individual cell could be isolated away from a cell crowd, then extracted out along with ~0.5μL phosphate buffered saline (PBS) via a pipette immediately after Raman spectral measurements of the same cell. As verification testing, we separated four different type of cells including BGC823 gastric cancer cells, erythrocytes, lymphocytes and E. coli cells, and quantifiably characterized the heterogeneity of the cancer cells, leukocyte subtype, and erythrocyte status, respectively. The average time of identifying and isolating a specific cell was 3 minutes. Cell morphology comparison and viability tests shown the successful rate of single-cell isolation was about 90%. Thus we believe our platform could further couple other single-cell techniques such as singlecell sequencing and become a multi-perspective analytical approach at the level of a single cell.
The dipole polarizabilities of the ground state ns 2 1 S 0 and the metastable state nsnp 3 P 0 ar... more The dipole polarizabilities of the ground state ns 2 1 S 0 and the metastable state nsnp 3 P 0 are crucial for estimating the light shifts and blackbody radiation shifts in the optical frequency standard based on alkalineearth-metal-like atoms. In this paper, the correlative dipole polarizabilities for group IIB atoms were calculated by the method of the B-spline configuration interaction with a semiempirical core-polarization model potential. The results are consistent with the experimental values in a reasonable accuracy and agree with other theoretical results as well. With these results, the magic wavelengths, at which the lowest-order light shift of the clock transition ns 2 1 S 0-nsnp 3 P 0 is null, were also obtained. For Zn, Cd, and Hg, they are 413, 420, and 363 nm, respectively.
Abstract Microsphere-assisted super-resolution imaging (MSI) is a label-free and wide-field imagi... more Abstract Microsphere-assisted super-resolution imaging (MSI) is a label-free and wide-field imaging technique, which draws much attention in the field. Here, a novel characteristic of MSI was reported. We demonstrated microsphere-assisted microscope possesses certain tomographic ability in the imaging of multilayer structure sample, Blu-ray disc (BD), resolving both periodic stripes and sub-surface recording marks which locate at different lays on BD, and performs the best vertical resolving under a short-wavelength illumination. Moreover, the magnification generated by microsphere and the lateral resolution in MSI, as well as their relationship, were discussed. Furthermore, our experiments show that a higher relative refractive index between the microsphere and immersion medium brings greater magnification, rather than better resolution, and theoretical simulation suggests that narrower beam waist focused by microsphere leads to better resolution in MSI.
Frequency is the most accuracy measurement quantity in the nature.Frequency Standards is the stan... more Frequency is the most accuracy measurement quantity in the nature.Frequency Standards is the standard of frequency measurement,it based on atomic transfer spectra lines which is high accuracy and stability.In the study of frequency standards there are almost problems of atomic physics,such as atomic structure and spectroscopy,interaction between atom and electronic and magnetic fields,and atom collision processes.In this paper the basic principle and application of frequency standards was given,and the atomic physical problem relative to frequency standards was briefly reviewed.
Drug resistance and heterogeneous characteristics of human gastric carcinoma cells (BGC823) under... more Drug resistance and heterogeneous characteristics of human gastric carcinoma cells (BGC823) under the treatment of paclitaxel (PTX) were investigated using single-cell Raman spectroscopy (RS). RS of normal and drug-resistant BGC823 cells (DR-BGC823) were collected and analyzed using arithmetic, statistic and individual spectrum analysis. The dynamic effects of paclitaxel (PTX) in normal and DR-BGC823 cells were evaluated dynamically. The RS intensity changed with PTX over time and produced distinct different results for the two types of cells. The average RS intensities of the normal BGC823 cells initially decreased and then increased under PTX treatment after 24 hours. In contrast, upon exposure to PTX, the average intensity of the DR-BGC823 cells initially increased within 12 hours and then gradually decreased and approached a steady state. The temporal variation of the typical component in the cells was analyzed by comparing the ratios between Raman bands. More importantly, the heterogeneous characteristics of the BGC823 cells under PTX treatment were quantified and clustered using hierarchical trees combined with RS intensity changes. The 'outlier' cells related to drug resistance were discriminated. The heterogeneity of the normal BGC823 cells under drug treatment gradually appeared over time, and was evaluated with the eigenvalues of principal component analysis (PCA). Our study indicates that single-cell RS may be useful in systematically and dynamically characterizing the drug response of cancer cells at the single-cell level.
Editorial on the Research Topic Quantum precision measurement and cold atom physics Ever since th... more Editorial on the Research Topic Quantum precision measurement and cold atom physics Ever since the invention of the cesium beam atomic clock in 1955, quantum frequency standards have seen considerable development over the decades, as a representative of quantum precision measurement. The progress in frequency measurements achieved in the past allows one to perform measurements of other physical and technical quantities with unprecedented precision, whenever they could be traced back to frequency measurements. Using atomic transitions as frequency references, quantum frequency standards are far less susceptible to external perturbations, and the quantum identity principle of microscopic particles allows easy replication of quantum frequency standards with the same frequency at any time and place. With laser cooling and trapping, cold atomic ensembles eliminate Doppler shift broadening and have become the go-to quantum reference when precision is required. The advancement of laser cooling and cold atom physics, in addition to novel physical matter states such as Bose-Einstein Condensation, gives rise to new experimental techniques in quantum precision measurement, especially quantum frequency standards, such as cesium fountain clocks dictating the SI second, as well as optical lattice clocks and single-ion optical clocks pushing the Frontier of Quantum Metrology. Other areas of quantum metrology, such as gravitometers and magnetometers, also benefit greatly from cold atoms. Challenges still remain, as researchers strive to push forward the limit in quantum precision measurement and search for novel physical phenomena in cold atomic systems. In this regard, we organized the Research Topic "Quantum Precision Measurement and Cold Atom Physics" in Frontiers in Physics. As a tribute to his 90th birthday on September 20, we dedicate this Research Topic to the venerable Prof. Yiqiu Wang, a pioneering figure in China's development of quantum precision measurement and cold atom physics. Chen et al. chronicled the scientific career
Intermolecular interactions dominate the behavior of signal transduction in various physiological... more Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (≈35 pN and ≈90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in ≈10−30 pN alterations in Ras-BRaf intermolecular binding force. The magnitude of changes in Ras-BRaf binding force correlates with the size of alterations in protein affinity and in α-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptor (-R)-mediated synaptic transmission in neurons expressing replacement BRaf mutants, and predicts the extent of learning impairments in animals expressing replacement BRaf mutants. These results establish single-molecule force spectroscopy as an effective platform for evaluating the piconewton-level interaction of signaling molecules and predicting the behavior outcome of signal transduction. Intermolecular interactions hold the key to understanding of the behavior of signal transduction mediating various physiological and pathological cell processes, yet precisely assessing the interactions of signaling effectors remains a daunting task. [1,2] Biochemical assays are the frequently used to evaluate the interactions since it directly measures the binding affinity of signaling effectors, although the approach often requires bulk samples and has limited resolution. [3-7] Recently, the evolution-and/or structure-based computational modeling has emerged as an alternative approach to estimate protein-protein interactions, but the calculation may not always achieve the desired accuracy, and can be sometimes challenging. [2,8,9] Single-molecule force spectroscopy, such as optical and magnetic tweezers, have been used as a powerful toolbox to investigate the forces and motions associated with cytoskeletal motors, ligand-receptor pairs, DNAs, RNAs, and viruses. [10-14] However, whether this piconewton resolution approach may be adapted for dissecting inter-molecular interactions and interrogating signal transduction behavior is still unclear. Rapid advances in genetic and genomics-sequencing techniques have identified nearly complete lists of genes and gene products involved in the major signaling networks in living organisms and associated large numbers of mutations on the genes with many human diseases. [15-20] However, these gene products and mutations alone reveal relatively little about regulation of signaling networks and pathogenesis of human diseases. For example, an extensive amount of early work has led to the definition of several key signaling components in the canonical MAPK pathway that mediates growth, proliferation, differentiation, oncogenesis, cognition, and mental illness. [2,17,18] In neuronal cells, this MAPK pathway Lim et al.
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