Nanotechnology Research Center, Department of Experimental and Clinical Medicine, University of "Magna Graecia", Catanzaro 88100, Italy.
J Biomech. 2021 Dec 2;129:110814. doi: 10.1016/j.jbiomech.2021.110814. Epub 2021 Oct 15.
Understanding and controlling the mechanisms of cell adhesion to nanomaterials is essential in tissue engineering, regenerative medicine, the development of experimental models for the study of neurodegenerative diseases. Nonetheless, despite the great many of studies that have examined how cells interact with nanoscale surfaces, little is known about the temporal dimension of the process of adhesion. In a previous work, Decuzzi and Ferrari, by examining how the energy of a cell changes while binding to a nanoscale surface, determined a criterion to decide whether nanoroughness can either enhance or retard cell adhesion. While accurate, however their model template disregards the time variable. Here, starting from the work of Decuzzi and Ferrari, we have developed a mathematical model based on chemotaxis that describes how cells adhere to a nanorough surface over time. Relaxing the originating constraint of a fixed density of ligand molecules expressed by the cell membrane, we show that the strength of adhesion depends on time and that, for certain values of the model parameters, a cell can arrive to establish a stable adhesion to a substrate even if the process of binding is initially energetically unfavourable. We show that, for a cell-membrane stiffness of 10kPa, an initial density of receptors of 500bonds/μm, a specific and non-specific energy density of adhesion of 10J/m and 10J/m, and roughness in the low nanometer range, cell adhesion forces can be completely activated from few seconds to some tens of minutes from the initial contact with the surface.
理解和控制细胞与纳米材料的黏附机制在组织工程、再生医学以及神经退行性疾病研究实验模型的开发中至关重要。尽管已经有大量研究探讨了细胞如何与纳米级表面相互作用，但对于黏附过程的时间维度知之甚少。在之前的研究中，Decuzzi 和 Ferrari 通过研究细胞与纳米级表面结合时能量的变化，确定了一个标准来判断纳米粗糙度是增强还是延迟细胞黏附。然而，尽管他们的模型模板准确无误，但却忽略了时间变量。在这里，我们从 Decuzzi 和 Ferrari 的工作出发，基于趋化性开发了一个数学模型，描述了细胞随时间黏附到纳米粗糙表面的过程。放宽细胞膜上表达的配体分子密度固定的初始约束条件，我们表明黏附强度取决于时间，并且对于模型参数的某些值，即使结合过程最初在能量上不利，细胞也可以到达并在基质上建立稳定的黏附。我们表明，对于细胞膜刚度为 10kPa、受体初始密度为 500 个/μm、特异性和非特异性黏附能量密度分别为 10J/m 和 10J/m，以及在低纳米范围内的粗糙度，从初始接触表面开始，细胞黏附力可以在几秒钟到几十分钟内完全激活。
