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分子刚度对膜锚定受体-配体结合动力学影响的理论与模拟研究

钟楚晗 徐光魁

钟楚晗, 徐光魁. 分子刚度对膜锚定受体-配体结合动力学影响的理论与模拟研究[J]. 应用数学和力学, 2021, 42(10): 1091-1102. doi: 10.21656/1000-0887.420262
引用本文: 钟楚晗, 徐光魁. 分子刚度对膜锚定受体-配体结合动力学影响的理论与模拟研究[J]. 应用数学和力学, 2021, 42(10): 1091-1102. doi: 10.21656/1000-0887.420262
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

分子刚度对膜锚定受体-配体结合动力学影响的理论与模拟研究

doi: 10.21656/1000-0887.420262
基金项目: 

国家自然科学基金(12072252)

详细信息
    作者简介:

    钟楚晗(1999—),女,硕士生(E-mail: zhongzhongchuhan@163.com);徐光魁(1986—),男,教授,博士,博士生导师(通讯作者. E-mail: guangkuixu@mail.xjtu.edu.cn).

    通讯作者:

    徐光魁(1986—),男,教授,博士,博士生导师(通讯作者. E-mail: guangkuixu@mail.xjtu.edu.cn).

  • 中图分类号: O34

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

Funds: 

The National Natural Science Foundation of China(12072252)

  • 摘要: 人体内大部分生物学过程都离不开细胞黏附.细胞黏附行为主要由锚定于细胞膜上的特异性分子(又称受体和配体)的结合动力学关系来决定.已有研究表明,特异性分子的结合关系受外力及细胞膜波动等多种因素影响.然而,特异性分子刚度对细胞膜锚定受体配体结合关系的影响机制仍不清楚.近期关于新冠病毒强传染力的研究表明,特异性黏附分子刚度对病毒与细胞结合具有重要影响.该文通过建立生物膜黏附的粗粒度模型,借助分子模拟和理论分析来研究分子刚度在黏附中的作用.结果表明,始终存在一个最佳膜间距及最佳分子刚度值,使得黏附分子亲和力和结合动力学参数达到最大值.这项研究不仅能加深人们对细胞黏附的认知,还有助于指导药物设计、疫苗研发等.
  • [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.
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出版历程
  • 收稿日期:  2021-09-02
  • 修回日期:  2021-09-18

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