Ralph E. Martin Department of Chemical Engineering, University of Arkansas, 3202 Bell Engineering Center, Fayetteville, AR, 72701, USA.
Department of Chemical, Biochemical, and Environmental Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
Soft Matter. 2024 Nov 20;20(45):8997-9006. doi: 10.1039/d4sm00534a.
Collagen is a key component of the extracellular matrix (ECM) and well-oriented domains of collagen are important for mimicking the local cell environment . While there has been significant attention directed towards the alignment of collagen, formation of large-scale oriented domains remains a key challenge. Type I collagen self-assembles to form liquid crystalline (LC) mesophases in acidic conditions at concentrations above 100 mg mL. The LC mesophase provides an efficient platform for large-scale alignment and patterning of collagen coated substrates. However, there still exist challenges related to solubilizing and processing of collagen at such high concentrations in order to replicate the native ECM. In this contribution, we report on centimeter-scale alignment in collagen-coated glass substrates using solutions that are well below the LC-forming concentrations. Importantly, we are also able to extend this method to macroscopic 3-D LC-collagen hydrogels with programmed anisotropy within them to create a mimic of the native ECM. We show that the orientation and aspect ratio of human Schwann cells are strongly coupled with the alignment of the collagen substrate/hydrogel. We use a simple model to estimate the critical magnetic field strength needed for a given concentration of collagen to permit macroscopic alignment-enabling guidance for future studies on alignment of collagen at high concentrations.
胶原蛋白是细胞外基质（ECM）的主要成分，而胶原蛋白的有序区域对于模拟局部细胞环境非常重要。虽然已经有大量的注意力集中在胶原蛋白的排列上，但形成大规模有序区域仍然是一个关键挑战。在酸性条件下，浓度高于 100mg/mL 时，I 型胶原蛋白会自组装形成液晶（LC）中间相。LC 中间相为胶原蛋白涂层基底的大规模排列和图案化提供了一个有效的平台。然而，在如此高的浓度下，仍然存在着与胶原蛋白的溶解和加工相关的挑战，以复制天然的 ECM。在本研究中，我们报告了在低于 LC 形成浓度的溶液中使用胶原蛋白涂覆的玻璃基底上进行厘米级别的排列。重要的是，我们还能够将这种方法扩展到具有内部各向异性的宏观 3D LC-胶原水凝胶中，以创建天然 ECM 的模拟物。我们发现，人雪旺细胞的取向和纵横比与胶原基底/水凝胶的排列密切相关。我们使用一个简单的模型来估计给定浓度的胶原蛋白所需的临界磁场强度，以实现宏观排列，为未来在高浓度下研究胶原蛋白排列提供指导。
