Materials Science and Engineering Division, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD, 20899, United States of America.
Biomed Mater. 2018 Jan 30;13(2):025012. doi: 10.1088/1748-605X/aa9650.
In living systems, it is frequently stated that form follows function by virtue of evolutionary pressures on organism development, but in the study of how functions emerge at the cellular level, function often follows form. We study this chicken versus egg problem of emergent structure-property relationships in living systems in the context of primary human bone marrow stromal cells cultured in a variety of microenvironments that have been shown to cause distinct patterns of cell function and differentiation. Through analysis of a publicly available catalog of three-dimensional (3D) cell shape data, we introduce a family of metrics to characterize the 'form' of the cell populations that emerge from a variety of diverse microenvironments. In particular, measures of form are considered that are expected to have direct significance for cell function, signaling and metabolic activity: dimensionality, polarizability and capacitance. Dimensionality was assessed by an intrinsic measure of cell shape obtained from the polarizability tensor. This tensor defines ellipsoids for arbitrary cell shapes and the thinnest dimension of these ellipsoids, P , defines a reference minimal scale for cells cultured in a 3D microenvironment. Polarizability governs the electric field generated by a cell, and determines the cell's ability to detect electric fields. Capacitance controls the shape dependence of the rate at which diffusing molecules contact the surface of the cell, and this has great significance for inter-cellular signaling. These results invite new approaches for designing scaffolds which explicitly direct cell dimensionality, polarizability and capacitance to guide the emergence of new cell functions derived from the acquired form.
在生命系统中，经常有人说，由于进化对生物体发育的压力，形式遵循功能，但在研究细胞水平的功能如何出现时，功能往往遵循形式。我们在原发性人骨髓基质细胞的培养环境中研究了这种结构-性质关系的涌现性问题，这些细胞培养在各种微环境中，这些微环境已被证明会导致细胞功能和分化的明显模式。通过对三维（3D）细胞形状数据的公共目录进行分析，我们引入了一系列指标来描述各种不同微环境中出现的细胞群体的“形式”。特别是，考虑了一些预计对细胞功能、信号转导和代谢活性具有直接意义的形态度量：维度、极化率和电容。通过从极化率张量中获得的细胞形状的内在度量来评估维度。该张量为任意细胞形状定义了椭球体，这些椭球体的最薄维度 P 定义了细胞在 3D 微环境中培养的参考最小尺度。极化率控制着细胞产生的电场，并决定了细胞检测电场的能力。电容控制着扩散分子与细胞表面接触的速率的形状依赖性，这对细胞间信号传递具有重要意义。这些结果为设计支架提供了新的方法，这些支架可以明确地指导细胞的维度、极化率和电容，以引导新的细胞功能的出现，这些功能源于所获得的形态。
