Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Isle Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
ACS Appl Mater Interfaces. 2020 May 20;12(20):22399-22409. doi: 10.1021/acsami.9b20939. Epub 2020 May 5.
Contact guidance has been extensively explored using patterned adhesion functionalities that predominantly mimic cell-matrix interactions. Whether contact guidance can also be driven by other types of interactions, such as cell-cell adhesion, still remains a question. Herein, this query is addressed by engineering a set of microstrip patterns of (i) cell-cell adhesion ligands and (ii) segregated cell-cell and cell-matrix ligands as a simple yet versatile set of platforms for the guidance of spreading, adhesion, and differentiation of mesenchymal stem cells. It was unprecedently found that micropatterns of cell-cell adhesion ligands can induce contact guidance. Surprisingly, it was found that patterns of alternating cell-matrix and cell-cell strips also induce contact guidance despite providing a spatial continuum for cell adhesion. This guidance is believed to be due to the difference between the potencies of the two adhesions. Furthermore, patterns that combine the two segregated adhesion functionalities were shown to induce more human mesenchymal stem cell osteogenic differentiation than monofunctional patterns. This work provides new insight into the functional crosstalk between cell-cell and cell-matrix adhesions and, overall, further highlights the ubiquitous impact of the biochemical anisotropy of the extracellular environment on cell function.
接触引导已经通过广泛使用图案化的粘附功能进行了探索，这些功能主要模拟细胞-基质相互作用。接触引导是否也可以由其他类型的相互作用驱动，例如细胞-细胞粘附，仍然是一个问题。在此，通过工程设计一组（i）细胞-细胞粘附配体和（ii）分离的细胞-细胞和细胞-基质配体的微带图案来解决这个问题，这是一组简单而通用的平台，用于引导间充质干细胞的扩展、粘附和分化。以前所未有的方式发现，细胞-细胞粘附配体的微图案可以诱导接触引导。令人惊讶的是，尽管为细胞粘附提供了空间连续性，但发现交替的细胞-基质和细胞-细胞条带的图案也可以诱导接触引导。这种引导被认为是由于两种粘附的效力不同所致。此外，组合两种分离的粘附功能的图案被证明比单功能图案更能诱导人骨髓间充质干细胞的成骨分化。这项工作提供了对细胞-细胞和细胞-基质粘附之间的功能串扰的新见解，并且总体上进一步强调了细胞外环境生化各向异性对细胞功能的普遍影响。
