Saha Asit K, Kohles Sean S
Center for Allaying Health Disparities through Research and Education (CADRE), Department of Mathematics and Computer Science, Central State University, Wilberforce, OH 45384.
J Nanotechnol Eng Med. 2010 Aug 1;1(3). doi: 10.1115/1.4001934.
Understanding physicochemical interactions during biokinetic regulation will be critical for the creation of relevant nanotechnology supporting cellular and molecular engineering. The impact of nanoscale influences in medicine and biology can be explored in detail through mathematical models as an in silico testbed. In a recent single-cell biomechanical analysis, the cytoskeletal strain response due to fluid-induced stresses was characterized (Wilson, Z. D., and Kohles, S. S., 2010, "Two-Dimensional Modeling of Nanomechanical Strains in Healthy and Diseased Single-Cells During Microfluidic Stress Applications," J. Nanotech. Eng. Med., 1(2), p. 021005). Results described a microfluidic environment having controlled nanometer and piconewton resolution for explorations of multiscale mechanobiology. In the present study, we constructed a mathematical model exploring the nanoscale biomolecular response to that controlled microenvironment. We introduce mechanical stimuli and scaling factor terms as specific input values for regulating a cartilage molecule synthesis. Iterative model results for this initial multiscale static load application have identified a transition threshold load level from which the mechanical input causes a shift from a catabolic state to an anabolic state. Modeled molecule homeostatic levels appear to be dependent upon the mechanical stimulus as reflected experimentally. This work provides a specific mathematical framework from which to explore biokinetic regulation. Further incorporation of nanomechanical stresses and strains into biokinetic models will ultimately lead to refined mechanotransduction relationships at the cellular and molecular levels.
了解生物动力学调节过程中的物理化学相互作用对于创建支持细胞和分子工程的相关纳米技术至关重要。纳米尺度影响在医学和生物学中的作用可以通过数学模型作为计算机模拟试验台进行详细探索。在最近的单细胞生物力学分析中，表征了流体诱导应力引起的细胞骨架应变响应（Wilson, Z. D., 和 Kohles, S. S., 2010, “微流体应力作用下健康和患病单细胞中纳米机械应变的二维建模”，《纳米技术工程与医学杂志》，1(2)，第 021005 页）。结果描述了一个具有可控纳米和皮牛顿分辨率的微流体环境，用于多尺度力学生物学的探索。在本研究中，我们构建了一个数学模型，探索对该可控微环境的纳米尺度生物分子响应。我们引入机械刺激和比例因子项作为调节软骨分子合成的特定输入值。对于这种初始多尺度静态载荷应用的迭代模型结果确定了一个转变阈值载荷水平，从该水平起机械输入会导致从分解代谢状态转变为合成代谢状态。模拟的分子稳态水平似乎如实验所反映的那样依赖于机械刺激。这项工作提供了一个用于探索生物动力学调节的特定数学框架。将纳米机械应力和应变进一步纳入生物动力学模型最终将在细胞和分子水平上导致更精确的机械转导关系。
