钙黏蛋白是一种细胞粘附分子，在维持生物体中组织形态发生和完整性方面起着至关重要的作用。如果粘附系统功能失调会对身体产生重大影响，比如癌症侵袭和转移、皮肤病、心肌病等疾病。然而，即使具有相似的晶体结构，它们的生物力学响应对于外部载荷也是不同的。因此，文中利用分子动力学软件包GROMACS2019。6模拟原子力显微镜探针在E-钙黏蛋白、N-钙黏蛋白和VE-钙黏蛋白上的纳米压痕，旨在从力学稳定性、粘附性和刚度的角度研究Ⅰ型和11型钙黏蛋白二聚体的生物力学响应。钙黏蛋白的胞外结构域被选为力学模型，因为它在控制细胞-细胞和细胞-底物相互作用中起着关键作用。结果表明，从均方根位移(root mean square displacement，RMSD)和力-位移曲线研究来看，E-钙黏蛋白二聚体与其他两种二聚体相比，其刚度最高，所以其具有较强的机械稳定性，RMSD波动也较小。而相比于其余两种二聚体，N-钙黏蛋白则是刚性较低，粘附性较强的，所以其RMSD波动也相对较大，机械稳定性较差。这一结果将有助于用更合适的基质培养不同的干细胞，并有助于解释体内细胞粘附强度的差异。
Molecular dynamics simulation of biomechanical response of type Ⅰ and type Ⅱ cadherin dimers
Cadherin,as a type of cell adhesion molecules,plays a crucial role in maintaining the morphogenesis and the integrity of tissues in organisms.Dysfunctional adhesion system will lead to a significant impact on the body,such as cancer invasion and metastasis,skin diseases,cardiomyopathy and other diseases.However,their biomechanical responses are various to external loads even with similar crystal structures.Therefore,this paper stimulates an atomic force microscopy probe nanoindentation on E-cadherin,N-cadherin and VE-cadherin using molecular dynamics software package GROMACS2019.6,aiming to study biomechanical response of type Ⅰ and type Ⅱ cadherin dimers in the perspective of mechanics stability,adhesion and stiffness.The extracellular domain of cadherin is selected as mechanics model since it plays a critical role in controlling cell-cell and cell-substrate.The results show that from the study of root mean square displacement(RMSD)and force displacement curve,E-cadherin dimer has the highest stiffness compared with the other two kinds of dimers,so it has strong mechanical stability,and RMSD fluctuation is small.Compared with the other two dimers,N-cadherin has lower rigidity and stronger adhesion,so its RMSD fluctuation is relatively large and its mechanical stability is poor.This result will shed light on the cultivation of different stem cells with more suitable matrices,and contributes to the interpretation of the differences in cell adhesion strength in vivo.
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