Modulation of Macro and Micro Mechanics of ECM by DDR1

DDR1对ECM宏观和微观力学的调制

• 批准号: 1201111
• 负责人: Gunjan Agarwal
• 金额: $ 38万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1201111&HistoricalAwards=false
• 关键词: Modulation; Macro; Micro; Mechanics; ECM

The research objective of this award is to use a combination of biophysical and computational tools to investigate the mechanics of the extracellular matrix (ECM) and how it is modified by proteins secreted by the cells. The ECM in most vertebrate tissue is composed primarily of collagen type 1 fibers. The structure of collagen fibers can be modulated by a number of collagen binding proteins. The proposed studies will evaluate the effect of such ultra-structural modifications in collagen fibers on the mechanical properties of the 3D matrix and on cell-matrix interactions at the macro and micro-scale levels using optical tweezers, uniaxial testing and gel contraction. In parallel, a multi-scale computational model will be developed to model the global and local mechanical responses of the collagen fiber matrix to uniaxial stress and traction forces exerted by the cells. If successful, these studies will provide novel insights into how naturally-induced alterations in the collagen ultra-structure can affect matrix mechanics, cell-matrix interaction and mechano-transduction. These results will impact the biophysics, biomechanics, biomaterials, and tissue engineering communities. The proposed activities will also develop novel methodologies for experimental and computational studies of the ECM. The educational plan will train two PhD-level graduate students with a diverse set of knowledge and hands-on skills in cell and matrix biology, microscopy, mechanical testing, instrument design, modeling and simulation, thus preparing them to meet the upcoming scientific challenges and tackle complex problems at the interface of engineering and biology. A new workshop on biomechanics is planned for middle school girls.

该奖项的研究目标是使用生物物理和计算工具的组合来研究细胞外基质(ECM)的机制，以及细胞分泌的蛋白质如何对其进行修饰。大多数脊椎动物组织中的细胞外基质主要由1型胶原纤维组成。胶原纤维的结构可以由许多胶原结合蛋白来调节。拟议的研究将使用光钳、单轴测试和凝胶收缩来评估胶原纤维中的这种超结构修饰对3D基质的机械性能以及宏观和微观水平上细胞-基质相互作用的影响。同时，将开发一个多尺度计算模型来模拟胶原纤维基质对细胞施加的单轴应力和牵引力的全局和局部力学响应。如果成功，这些研究将为自然诱导的胶原超结构变化如何影响基质力学、细胞-基质相互作用和机械转导提供新的见解。这些结果将影响生物物理学、生物力学、生物材料和组织工程领域。拟议的活动还将为环境管理的实验和计算研究开发新的方法。该教育计划将培养两名博士生，他们在细胞和基质生物学、显微镜、机械测试、仪器设计、建模和模拟方面拥有不同的知识和动手技能，从而使他们做好准备，迎接即将到来的科学挑战，并在工程和生物学的交界处解决复杂的问题。计划为中学女生举办一个新的生物力学研讨会。

项目成果

Role of DDR2 ECD Oligomerization in Binding to Collagen

• DOI: 10.1017/s1431927616006474
• 发表时间: 2016-07
• 期刊: Microscopy and Microanalysis
• 影响因子: 2.8
• 作者: Carolyn Wang;D. Yeung;Jack Wellerming;A. Herr;Jeanette L. C. Miller;R. Fridman;G. Agarwal

Collagen Ultrastructure and Skin Mechanics in DDR1 KO Mice

DDR1 KO 小鼠的胶原超微结构和皮肤力学

• DOI: 10.1017/s1431927613002547
• 发表时间: 2013
• 期刊: Microscopy and Microanalysis
• 影响因子: 2.8
• 作者: Yeung, D.;Chen, S.;Tonniges, J.;Lee, J.;Powell, H.;Calomeni, E.;Agarwal, G.
• 通讯作者: Agarwal, G.