Collaborative Research: Utilization of Smart Materials and Predictive Modeling to Integrate Intracellular Dynamics with Cell Biomechanics and Collective Tissue Behavior

该研究项目的目标是利用生物材料科学领域的可编程材料、生物力学和生物物理学领域的粒子跟踪算法以及细胞和分子生物学领域的分子探针来跟踪和模拟细胞内多种成分的相互作用和由此产生的大规模细胞行为。生物力学和机械生物学的一个重大挑战是理解细胞内结构之间发生的复杂相互作用，以及这些相互作用如何在细胞和组织水平上产生功能。通过三个目标，该项目将产生一种方法，用于定量描述细胞内成分之间的相互作用，并将这些模式与细胞极化等大规模行为联系起来。首先，细胞内极化的生物力学序列将通过在高度受限的环境中对单个细胞中的多个成分进行自动、同步跟踪来阐明。其次，使用智能底物将在单个细胞中诱导细胞极化，细胞内成分的模式将与这种大规模细胞行为联系在一起。第三，细胞极化的研究和模拟，从细胞内到多细胞水平，在高细胞密度的接触抑制释放/局部上皮-间充质转变的模型中。协调的细胞运动对胚胎发育、癌症进展和伤口愈合等生物过程至关重要。虽然细胞运动是由细胞内的结构产生的，但这些结构的相互作用如何产生细胞运动和细胞群内的组织尚不清楚。这个项目将回答这个问题。一种新的计算方法将量化细胞内几个不同重要结构的同时相互作用。新的智能材料将被用来触发细胞运动的变化，计算方法将确定细胞内结构的相互作用也将如何变化。低细胞密度和高细胞密度都将被研究，低细胞密度是细胞很少相互作用的地方，高细胞密度是细胞总是接触的，就像在活的有机体中发生的那样。将开发一种能够预测组织形成和疾病的大群体细胞集体运动模型。社会将受益于相关个人的技术和专业发展，生物力学、生物物理学和生物学领域的重大进展，以及医疗保健领域有望取得的突破。这两个合作机构的研究、教育和多样性将通过一年一度的暑期研究计划进一步整合，该计划将招募优秀的汉普顿大学学生作为本科生。

The goal of this research project is to employ programmable materials from the field of biomaterials science, particle-tracking algorithms from the fields of biomechanics and biophysics, and molecular probes from the fields of cell and molecular biology to track and model the interaction of multiple intracellular components and the resultant large-scale cellular behaviors. A grand challenge in biomechanics and mechanobiology is that of understanding the complex interactions that occur between intracellular structures and how those interactions produce function at the cell and tissue levels. Through three objectives, this project will yield a method for quantitatively characterizing interactions between intracellular components and linking those patterns with large-scale behaviors such as cell polarization. First, the biomechanical sequence of cell polarization at the intracellular level will be elucidated via automated, synchronized tracking of multiple components in single cells in highly constrained environments. Second, cell polarization will be induced in individual cells using smart substrates and patterns in intracellular components will be linked to this large-scale cell behavior. Third, cell polarization will be studied and modeled, from the intracellular to multicellular levels, in a model of contact inhibition release/localized epithelial-mesenchymal transition with high cell densities. Coordinated cell movements are critical to biological processes such as embryonic development, cancer progression, and wound healing. Although cell movement is generated by structures inside cells, it is not known how interactions of those structures produce cell movement and resulting organization within groups of cells. This project will answer that question. A new computational approach will quantify the simultaneously interactions of several different important structures inside cells. New smart material will be used to trigger changes to cell movement, and the computational approach will determine how interactions of structures inside cells also change. Both low cell densities, where cells interact rarely, and high cell densities, where cells are always touching as happens in living organisms, will be studied. A model for collective movement of large groups of cells that can make predictions about tissues formation and disease will be developed.Society will benefit from the technical and professional development of the individuals involved, important advances in the fields of biomechanics, biophysics, and biology, and breakthroughs that can be anticipated in healthcare fields. Research, education, and diversity at both collaborating institutions will be further integrated through a yearly summer research program that will recruit exceptional Hampton University students as undergraduate researchers.