Volume 42 Issue 10
Oct.  2021
Turn off MathJax
Article Contents
ZHONG Chuhan, XU Guangkui. Theoretical and Simulation Studies on the Effect of Molecular Stiffness on Binding Kinetics of Membrane-Anchored Receptors And Ligands[J]. Applied Mathematics and Mechanics, 2021, 42(10): 1091-1102. doi: 10.21656/1000-0887.420262
Citation: ZHONG Chuhan, XU Guangkui. Theoretical and Simulation Studies on the Effect of Molecular Stiffness on Binding Kinetics of Membrane-Anchored Receptors And Ligands[J]. Applied Mathematics and Mechanics, 2021, 42(10): 1091-1102. doi: 10.21656/1000-0887.420262

Theoretical and Simulation Studies on the Effect of Molecular Stiffness on Binding Kinetics of Membrane-Anchored Receptors And Ligands

doi: 10.21656/1000-0887.420262
Funds:

The National Natural Science Foundation of China(12072252)

  • Received Date: 2021-09-02
  • Rev Recd Date: 2021-09-18
  • Cell adhesion plays an important role in most biological processes in human body. Cell adhesion is mainly determined by the binding kinetics of specific molecules (called receptors and ligands) anchored on the cell membrane. Although it is known that the binding relation of specific molecules is affected by various factors as external forces and cell membrane fluctuations, it is still unclear how the molecular stiffness affects the binding relation between the membrane-anchored receptors and ligands. Recent studies on the strong infectivity of the coronavirus have shown the importance of specific molecular stiffness to the adhesion between virus and cells. Here, we develop a coarse-grained model of biomembrane adhesion, and use molecular simulation and theoretical analysis to reveal the role of molecular stiffness in adhesion. The results show that there is always an optimal membrane and an optimal molecular stiffness value, and the adhesion molecular affinity and binding kinetic parameters reach the maximum. This study can not only deepen the understanding of cell adhesion, but also help guide drug design and vaccine development.
  • loading
  • [2]BURRIDGE K, CHRZANOWSKA-WODNICKA M. Focal adhesions, contractility, and signaling[J].Annual Review of Cell and Developmental Biology,1996,12(1): 463-519.
    ALBERTS B, JOHNSON A, LEWIS J, et al.Molecular Biology of the Cell[M]. New York: Garland Science Press, 2002.
    [3]GEIGER B, BERSHADSKY A, PANKOV R, et al. Transmembrane extracellular matrix-cytoskeleton crosstalk[J].Nature Reviews Molecular Cell Biology,2001,2(11): 793-805.
    [4]XU G K, QIAN J, HU J. The glycocalyx promotes cooperative binding and clustering of adhesion receptors[J].Soft Matter,2016,12(20): 4572-4583.
    [5]戎伟峰,王如彬. 耳蜗毛细胞活动的神经动力学分析[J]. 应用数学和力学,2019,40(2): 139-149.(PANG Weifeng, WANG Rubin. Neurodynamic analysis of cochlear hair cell activity[J].Applied Mathematics and Mechanics,2019,40(2):139-149.(in Chinese))
    [6]Bongrand P. Ligand-receptor interactions[J].Reports on Progress in Physics,1999,62(6): 921-968.
    [7]WEIKL T R, ASFAW M, KROBATH H, et al. Adhesion of membranes via receptor-ligand complexes: domain formation, binding cooperativity, and active processes[J].Soft Matter,2009,5(17): 3213-3224.
    [8]WU Y, VENDOME J, SHAPIRO L, et al. Transforming binding affinities from three dimensions to two with application to cadherin clustering[J].Nature,2011,475: 510-513.
    [9]BELL G I. Models for the specific adhesion of cells to cells[J].Science,1978,200(4342): 618-627.
    [10]DEMBO M, TORNEY D C, SAXMAN K, et al. The reaction-limited kinetics of membrane-to-surface adhesion and detachment[J].Proceedings of the Royal Society of London(Series B): Biological Sciences,1988,234(1274): 55-83.
    [11]ERDMANN T, SCHWARZ U S. Stability of adhesion clusters under constant force[J].Physical Review Letters,2004,92(10): 108102.
    [12]HUPPA J B, AXMANN M, MORTELMAIER M A, et al. TCR-peptide-MHC interactions in situ show accelerated kinetics and increased affinity[J].Nature,2010,463(7283): 963-967.
    [13]DUSTIN M L, BROMLEY S K, DAVIS M M, et al. Identification of self through two-dimensional chemistry and synapses[J].Annual Review of Cell and Developmental Biology,2001,17(1): 133-157.
    [14]MILSTEIN O, TSENG S Y, STARR T, et al. Nanoscale increases in CD2-CD48-mediated intermembrane spacing decrease adhesion and reorganize the immunological synapse[J].Journal of Biological Chemistry,2008,283(49): 34414-34422.
    [15]JEPPESEN C, WONG J Y, KUHL T L, et al. Impact of polymer tether length on multiple ligand-receptor bond formation[J].Science,2001,293(5529): 465-468.
    [16]KROBATH H, ROZYCKI B, LIPOWSKY R, et al. Binding cooperativity of membrane adhesion receptors[J].Soft Matter,2009,5(17): 3354-3361.
    [17]HU J, LIPOWSKY R, WEIKL T R. Binding constants of membrane-anchored receptors and ligands depend strongly on the nanoscale roughness of membranes[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(38): 15283-15288.
    [18]MULIVOR A W, LIPOWSKY H H. Role of glycocalyx in leukocyte-endothelial cell adhesion[J].American Journal of Physiology-Heart and Circulatory Physiology,2002,283(4): H1282-H1291.
    [19]PASZEK M J, DUFORT C C, ROSSIER O, et al. The cancer glycocalyx mechanically primes integrin-mediated growth and survival[J].Nature,2014,511(7509): 319-325.
    [20]LONG M, GOLDSMITH H L, TEES D F J, et al. Probabilistic modeling of shear-induced formation and breakage of doublets cross-linked by receptor-ligand bonds[J].Biophysical Journal,1999,76(2): 1112-1128.
    [21]MARSHALL B T, LONG M, PIPER J W, et al. Direct observation of catch bonds involving cell-adhesion molecules[J].Nature,2003,423(6936): 190-193.
    [22]LONG M, CHEN J, JIANG N, et al. Probabilistic modeling of rosette formation[J].Biophysical Journal,2006,91(1): 352-363.
    [23]XIAO B T, TONG C F, JIA X L, et al. Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane[J].Biophysical Journal,2012,103(4): 777-785.
    [24]QIAN J, WANG J Z, GAO H J. Lifetime and strength of adhesive molecular bond clusters between elastic media[J].Langmuir,2008,24(4): 1262-1270.
    [25]QIAN J, WANG J Z, LIN Y, et al. Lifetime and strength of periodic bond clusters between elastic media under inclined loading[J].Biophysical Journal,2009,97(9): 2438-2445.
    [26]LIU B, QU M J, QIN K R, et al. Role of cyclic strain frequency in regulating the alignment of vascular smooth muscle cells in vitro[J].Biophysical Journal,2008,94(4): 1497-1507.
    [27]KONG D, JI B H, DAI L H. Stability of adhesion clusters and cell reorientation under lateral cyclic tension[J].Biophysical Journal,2008,95(8): 4034-4044.
    [28]KONG D, JI B H, DAI L H. Stabilizing to disruptive transition of focal adhesion response to mechanical forces[J].Journal of Biomechanics,2010,43(13): 2524-2529.
    [29]HUANG J Y, QIN L, PENG X L, et al. Cellular traction force recovery: an optimal filtering approach in two-dimensional Fourier space[J].Journal of Theoretical Biology,2009,259(4): 811-819.
    [30]FANG Y, WU J H, MCEVER R P, et al. Bending rigidities of cell surface molecules P-selectin and PSGL-1[J].Journal of Biomechanics,2009,42(3): 303-307.
    [31]DU J, CHEN X F, LIANG X D, et al. Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity[J].Proceedings of the National Academy of Sciences of the United States of America,2011,108(23): 9466-9471.
    [32]XU G K, YANG C, DU J, et al. Integrin activation and internalization mediated by extracellular matrix elasticity: a biomechanical model[J].Journal of Biomechanics,2014,47(6): 1479-1484.
    [33]BARROS E P, CASALINO L, GAIEB Z, et al. The flexibility of ACE2 in the context of SARS-CoV-2 infection[J].Biophysical Journal,2021,120(6): 1072-1084.
    [34]KE Z L, OTON J, QU K, et al. Structures and distributions of SARS-CoV-2 spike proteins on intact virions[J].Nature,2020,588(7838): 498-502.
    [35]SERAPIAN S A, COLOMBO G. Bow to the enemy: how flexibility of host protein receptors can favor SARS-CoV-2[J].Biophysical Journal,2021,120(6): 977-979.
    [36]YAO H P, SONG Y T, CHEN Y, et al. Molecular architecture of the SARS-CoV-2 virus[J].Cell,2020,183(3): 730-738.
    [37]TURONOVA B, SIKORA M, SCHURMANN C, et al. In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges[J].Science,2020,370(6513): 203-208.
    [38]XU G K, HU J L, LIPOWSKY R, et al. Binding constants of membrane-anchored receptors and ligands: a general theory corroborated by Monte-Carlo simulations[J].The Journal of Chemical Physics,2015,143(24): 243136.
    [39]WEIKL T R, LIPOWSKY R. Membrane adhesion and domain formation[J].Advances in Planar Lipid Bilayers and Liposomes,2007,5(1): 63-127.
    [40]BINDER K, CEPERLEY D M, HANSEN J P, et al.Monte-Carlo Methods in Statistical Physics[M]. Springer Science & Business Media, 2012.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (867) PDF downloads(76) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return