Biomaterials Directed Cell Polarity and Migration

描述（由申请人提供）：细胞运动在组织形态发生、胚胎发育、血管生成和伤口愈合中起着核心作用。体外诱导定向细胞迁移、自下而上组织模式组装、伤口愈合和细胞芯片设备的主要技术依赖于外部梯度、趋化性。然而，由于细胞响应的梯度范围有限，控制大量细胞在长距离独立迁移仍然是一个挑战。在过去的资助期内，我们报道了用于引导细胞迁移的创新技术：2D表面微模式（MANDIP -自然定向持久性微阵列扩增）和3D微通道（TANDIP -自然定向持久性地形扩增）。没有梯度，MANDIP和TANDIP具有高度可扩展性，可以并行运行，在复杂路径上无限距离地引导大量细胞。这种能力的演示应用包括MANDIP定向的不同细胞群的空间自组装

DESCRIPTION (provided by applicant): Cell motility plays a central role in tissue morphogenesis, embryonic development, angiogenesis, and wound healing. The primary techniques for inducing directional cell migration in vitro, for bottom-up assembly of tissue patterns, wound healing, and cell- on-chip devices, rely on external gradients, chemotaxis. However, due to the finite range of gradients that cells respond to, steering the migration of large population of cells independently over long distances remains a challenge. Over the past funding period, we reported innovative techniques for guiding cell migration using: 2D surface micropatterns (MANDIP - Microarray Amplification of Natural Directional Persistence) and 3D microchannels (TANDIP - Topographical Amplification of Natural Directional Persistence). Free from gradients, MANDIP and TANDIP are highly scalable and can operate in parallel to direct large number of cells over unlimited distances on complex paths. Demonstrated applications of this capability include MANDIP directed self- assembly of different cell populations into spatially defined structures and sorting of cells by their intrinsic motility. Using MANDIP, TANDIP, and a new technique for fabricating substrates with light-switchable cell adhesiveness, we can now probe mechanistically how cells sense their surrounding extracellular matrix (ECM) to polarize and migrate directionally either along or against their initial morphological polarization. We also partnered with 4 collaborators at UC Medical School and Childrens Hospital who specialize in migration signaling pathways and cell polarity. In this first competitive renewal application, we will focus on understanding the sequence and interdependency of key events that occur during cell polarization and migration by addressing the following specific questions: Aim 1. How do local changes in attachment of lamellipodia alter morphological polarization? Aim 2. How do geometric cell-substrate interactions direct Golgi polarization? Aim 3. How do different cell types differ in their response to biomechanical cues?