Smart Substrates for Cell Biology and Tissue Engineering

描述(由申请者提供)：该研究计划将开发广泛类别的活性底物，用于细胞生物学的机械研究和组织工程中的应用。大多数哺乳动物细胞都是贴壁的，为了生存、增殖、分化和发挥功能，必须保持与蛋白质细胞外基质的附着。细胞与蛋白质基质的相互作用是由一系列细胞表面受体和基质衍生配体介导的，这些受体和基质衍生配体不仅可以定位细胞在组织中，还可以为细胞提供调节信号。在许多情况下，提示是动态调节的：也就是说，从基质中呈现的配体的组成随着时间的推移而变化。细胞和基质之间的动态相互作用的实验研究是困难的，仍然需要新的工具来模拟对细胞调控至关重要的复杂的相互作用模式。这项研究计划将开发一种创造动态底物的策略，其中固定化配体的活性可以在电子控制下实时切换。该计划将开发模型底物，其中：i)配体的活性可以被开启；ii)配体的活性可以被关闭；iii)配体的活性可以在高亲和力和低亲和力状态之间可逆地切换。该计划还将开发包含两种或两种以上这些特性的多功能基材。该计划将把这些活性底物应用于细胞生物学和组织工程中的一系列模型问题，以验证这些策略并实现计划目标，即提出一种对细胞生物学实验研究和组织工程技术有价值的方法。最后，该计划将制定战略，将这些活性底物过渡到生物和生物工程社区的用户。将开发可用各种配体修饰并结合用于动态控制配体活性的化学物质的各类底物，并验证其用途。这项计划将推进一项将在生物和医学的几个领域产生广泛影响的技术。

DESCRIPTION (provided by applicant): This research program will develop a broad class of active substrates for mechanistic studies in cell biology and applications in tissue engineering. Most mammalian cells are adherent and must remain attached to the protein extracellular matrix in order to survive, proliferate, differentiate and function. The interactions of cells with the protein matrix are mediated by a host of cell-surface receptors and matrix-derived ligands, which serve not only to localize cells in tissue but also to provide cells with regulatory cues. In many instances, the cues are dynamically modulated: that is, the composition of ligands presented from the matrix changes over time. Experimental studies of dynamic interactions between cell and matrix are difficult and still in need of new tools that can mimic the complex patterns of interactions that are central to cellular regulation. This research program will develop a strategy for creating dynamic substrates wherein the activities of immobilized ligands can be switched in real-time under an electrical control. The program will develop model substrates wherein: i) the activities of ligands can be switched on; ii) the activities of ligands can be switched off; iii) the activities of ligands can be reversibly switched between high and low affinity states. The program will also develop multifunctional substrates that incorporate two or more of these properties. The program will apply these active substrates to a set of model problems in cell biology and tissue engineering in order to validate these strategies and meet the program goals of advancing an approach that will be valuable to experimental studies in cell biology and technologies for engineering tissue. Finally, the program will develop strategies for transitioning these active substrates to users in the biological and bioengineering communities. Classes of substrates that can be modified with a variety of ligands and that incorporate the chemistries for dynamic control over ligand activity will be developed and validated for use. This program will advance a technology that will have broad impact across several areas in biology and medicine.