dimensionality controls cytoskeleton assembly and metabolism of fibroblast cells in response to rigidity and shape维度控制细胞骨架组装和成纤维细胞的代谢反应刚度和形状.pdfVIP

Dimensionality Controls Cytoskeleton Assembly and Metabolism of Fibroblast Cells in Response to Rigidity and Shape 1¤b 1 2 2 ¤a Mirjam Ochsner , Marcus Textor , Viola Vogel , Michael L. Smith * 1 BioInterface Group, Laboratory for Surface Science and Technology, ETH Zurich, Zurich, Switzerland, 2 Laboratory for Biologically Oriented Materials, ETH Zurich, Zurich, Switzerland Abstract Background: Various physical parameters, including substrate rigidity, size of adhesive islands and micro-and nano- topographies, have been shown to differentially regulate cell fate in two-dimensional (2-D) cell cultures. Cells anchored in a three-dimensional (3-D) microenvironment show significantly altered phenotypes, from altered cell adhesions, to cell migration and differentiation. Yet, no systematic analysis has been performed that studied how the integrated cellular responses to the physical characteristics of the environment are regulated by dimensionality (2-D versus 3-D). Methodology/Principal Findings: Arrays of 5 or 10 mm deep microwells were fabricated in polydimethylsiloxane (PDMS). The actin cytoskeleton was compared for single primary fibroblasts adhering either to microfabricated adhesive islands (2-D) or trapped in microwells (3-D) of controlled size, shape, and wall rigidity. On rigid substrates (Young’s Modulus = 1 MPa), cytoskeleton assembly within single fibroblast cells occurred in 3-D microwells of circular, rectangular, square, and triangular shapes with 2-D projected surface areas (microwell bottom surface area) and total surface areas of adhesion (microwell bottom plus wall surface area) that inhibited stress fiber assembly in 2-D. In contrast, cells did not assemble a detecta