Investigation of the adhesive characteristics of polymer-protein systems through molecular dynamics simulation and their relation to cell adhesion and proliferation
Investigation of the adhesive characteristics of polymer-protein systems through molecular dynamics simulation and their relation to cell adhesion and proliferation
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DOI：
10.1039/c6ib00159a
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发表时间：
2016-01-01
影响因子：
2.5
通讯作者：
Sarmadi, Morteza
中科院分区：
文献类型：
--
作者：
Shamloo, Amir;Sarmadi, Morteza
蛋白质粘附是一种普遍而复杂的现象，在生物材料暴露于生物系统后立即发生。生物材料-蛋白质系统粘附特性的研究遇到了严重的障碍，因为实验方法不能正确地捕捉到发生在纳/皮秒内的蛋白质粘附的初始阶段。这推动了利用计算方法来了解不同蛋白质和生物材料表面之间相互作用的研究。本文以分子动力学（MD）模型为计算框架，研究了不同生物材料-蛋白质体系的粘附特性。为此，包括两种合成高分子生物材料，即聚己内酯（PCL）和聚乙烯醇（PVA），广泛应用于组织工程。还考虑了四种蛋白质片段，包括两种细胞外基质（ECM）蛋白：ⅰ型胶原蛋白和纤维连接蛋白，以及人血清白蛋白（HSA）的两个亚结构域。随后，通过MD模拟计算黏附功和剥离力，量化了这些聚合物-蛋白质体系的黏附特性。在研究的下一阶段，我们将研究骨髓细胞在PCL和PVA纳米纤维组成的电纺丝支架上的细胞增殖和粘附，以了解从模拟中获得的蛋白质粘附特性与从实验中获得的细胞粘附和增殖之间的联系。结果表明，PCL疏水表面具有较强的蛋白质粘附性和较好的细胞增殖能力。然而，PVA表面仅对一个白蛋白亚结构域具有较好的粘附性。本研究结果表明，ECM蛋白与生物材料表面更强的粘附与更理想的细胞粘附和增殖之间存在直接联系。
Protein adhesion is a prevalent, however, intricate phenomenon that occurs immediately after exposure of a biomaterial to the biological system. A study on the adhesive characteristics of biomaterial-protein systems has encountered serious hurdles as experimental methods cannot properly capture the initial stages of protein adhesion, taking place within nano/picoseconds. This propels research studies toward utilizing computational approaches to gain an understanding of the interactions between different proteins and biomaterial surfaces. Herein, we use molecular dynamics (MD) modeling, as the computational framework, to study the adhesive characteristics of different biomaterial-protein systems. To this aim, two synthetic polymeric biomaterials, namely polycaprolactone (PCL) and polyvinyl alcohol (PVA), extensively used in tissue engineering are included. Four protein fragments are also considered including two extracellular matrix (ECM) proteins: collagen type-I, and fibronectin, along with two subdomains of human serum albumin (HSA). Subsequently, the adhesive characteristics of these polymer-protein systems were quantified by calculating the work of adhesion and peeling force through MD simulations. In the next phase of the study, cell proliferation and adhesion using bone marrow cells on electrospun scaffolds composed of PCL and PVA nanofibers were investigated to gain an understanding of the connection between the protein adhesion characteristics obtained from the simulations and cell adhesion and proliferation from an experimental assay. The results indicate that generally the hydrophobic surface of PCL represents both stronger protein adhesion and better cell proliferation. However, the PVA surface represents better adhesion only for one albumin subdomain. Results of this study demonstrate a direct connection between the stronger adhesion of ECM proteins to the biomaterial surface and more desirable cell adhesion and proliferation.