The Mechanobiology of 2D and 3D Multicellular Systems

2D 和 3D 多细胞系统的力学生物学

• 批准号: RGPIN-2019-05731
• 负责人: Pelling, Andrew
• 金额: $ 5.03万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738480
• 关键词: Mechanobiology; 2D; 3D; Multicellular; Systems

In the body, mammalian cells exist in a dynamic, three-dimensional microenvironment where numerous physical and biochemical cues interact to govern critical biological processes (e.g, stem cell fate, motility, mitosis, morphogenesis, etc.). Physical cues can include dynamic and time-dependent variations in local mechanical properties of the extra-cellular matrix (ECM), complex stresses and strains occurring in response to tissue stretching and compression during movement, or even changes in microenvironment shape and topography as a result of ECM remodelling and tissue movements. While cellular responses to biochemical molecules and gradients are well studied, the ability of cells to sense, integrate and respond to diverse and physical cues is not as well understood. To continue developing our understanding of mechanobiology, novel experimental protocols and devices are required to mimic the complexity of the cellular microenvironment. Such tools and related experimental approaches enable researchers to systematically expose cells to physical stimuli, measure their responses and uncover new knowledge. This leads to a deeper understanding of the critical role physical cues play in governing fundamental aspects of cell biology. We have been addressing these issues by engineering novel cell culture devices and approaches for exposing mammalian cells to systematically controlled physical stimuli. Utilizing these platforms, we have established experimental protocols to characterize some of the earliest structural responses of cells to changes in mechanical properties, microtopography and stress/strain occurring in the microenvironment. This has allowed elucidate how cells detect, integrate and respond to diverse physical stimuli and enhance our understanding of mechanobiology. These insights are allowing us to understand how complex physical stimuli are hard wired into underlying mechanobiological networks. These pathways have been shown to regulate normal healthy physiological processes and also appear to become disrupted in several disease pathologies. Importantly, our fundamental research has also been translated through commercialization, industry partnerships and licensed intellectual property. Our discoveries are driving innovation through the creation of new biomedical devices and technologies, as well as applications in bioengineering, cell bioprocessing, tissue engineering and regenerative medicine.

在体内，哺乳动物细胞存在于动态的三维微环境中，其中许多物理和生化线索相互作用以控制关键的生物过程（例如，干细胞命运、运动性、有丝分裂、形态发生等）。物理线索可以包括细胞外基质（ECM）的局部机械性质的动态和时间依赖性变化、响应于运动期间的组织拉伸和压缩而发生的复杂应力和应变、或者甚至由于ECM重塑和组织运动而导致的微环境形状和形貌的变化。虽然细胞对生物化学分子和梯度的反应得到了很好的研究，但细胞感知、整合和响应各种物理线索的能力还没有得到很好的理解。为了继续发展我们对机械生物学的理解，需要新的实验方案和设备来模拟细胞微环境的复杂性。这些工具和相关的实验方法使研究人员能够系统地将细胞暴露于物理刺激，测量它们的反应并发现新的知识。这导致对物理线索在管理细胞生物学基本方面的关键作用有了更深入的理解。我们一直致力于解决这些问题的工程新的细胞培养设备和方法，使哺乳动物细胞系统控制的物理刺激。利用这些平台，我们已经建立了实验方案，以表征细胞对微环境中发生的机械性能，微观形貌和应力/应变变化的一些最早的结构反应。这使得阐明细胞如何检测，整合和响应不同的物理刺激，并增强我们对机械生物学的理解。这些见解使我们能够理解复杂的物理刺激如何与潜在的机械生物学网络紧密相连。这些途径已被证明可以调节正常的健康生理过程，并且似乎在几种疾病病理中被破坏。重要的是，我们的基础研究也通过商业化，行业合作伙伴关系和许可知识产权进行了转化。我们的发现正在通过创造新的生物医学设备和技术，以及在生物工程，细胞生物加工，组织工程和再生医学中的应用来推动创新。