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Models for cellular force generation and the cell-substrate interface

细胞力产生和细胞-基质界面模型

基本信息

批准号：
1944689
负责人：
金额：
--
依托单位：
University of Surrey
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1944689
关键词：
Models cellular force generation cell

项目摘要

Cells are able to interact with their environments through a variety of chemical and physical signalling mechanisms, with it becoming increasingly clear that physical force plays a crucial role in determining cellular behaviour and coordination. It is clear that cells respond very differently depending on the mechanical properties of their environments; understanding these differences in their behaviour is crucial for tissue engineering applications and to understand how the mechanical microenvironment may affect, for example, cancer growth and invasion.This project focuses on developing advanced mathematical models to describe the physical forces exerted by a single cell or cell layer when adhered to a gel layer and to elucidate the complex interplay between cellular dynamics and the mechanical microenvironment. The model context focuses on the most common biophysical experimental set-ups for investigating cellular forces. These experiments generally work from inferring cellular forces from measurements of the observed substrate deformation, using experimentally determined knowledge of the mechanical response of the designed substrates. The underlying substrates range from elastic gels (as for Traction Force Microscopy studies) to arrays of micropillars.The modelling framework being developed is based in continuum elasticity theory additionally using active matter theory to describe cellular contractility, which is the primary mechanism of force generation. On the time scale of experimental observations the cell or cell layer is assumed to be in mechanical equilibrium. This project is developing detailed mathematical descriptions of the cell-gel interface and also of the mechanisms of force generation. A key objective is to explain the observed cellular adaptations to changes in the mechanical properties of the underlying gel. The models are being analysed and solved using both analytical approaches (exploiting approximations and symmetry arguments) and using Finite Element Methods.

细胞能够通过各种化学和物理信号机制与环境相互作用，越来越明显的是，物理力量在决定细胞行为和协调方面发挥着关键作用。很明显，细胞对环境的机械属性的反应非常不同；了解它们行为上的这些差异对于组织工程应用和了解机械微环境如何影响例如癌症的生长和侵袭至关重要。本项目专注于开发高级数学模型来描述单个细胞或细胞层在附着到凝胶层时所施加的物理力，并阐明细胞动力学和机械微环境之间的复杂相互作用。模型内容集中在用于研究细胞力的最常见的生物物理实验装置上。这些实验通常是利用实验确定的设计基板的机械响应知识，根据观察到的基板变形的测量结果来推断细胞力。底物范围从弹性凝胶(如牵引力显微镜研究)到微柱阵列。正在开发的建模框架基于连续介质弹性理论，此外还使用活性物质理论来描述细胞的收缩能力，这是力产生的主要机制。在实验观察的时间尺度上，假定细胞或细胞层处于机械平衡状态。该项目正在开发细胞-凝胶界面以及力产生机制的详细数学描述。一个关键的目标是解释观察到的细胞对底层凝胶机械性能变化的适应性。正在使用分析方法(利用近似和对称论点)和使用有限元方法来分析和求解这些模型。