生理与病理条件下生物组织生长发育的多尺度力学理论及其应用

无论是在正常生理条件下的生长发育，还是在疾病情况下的病变演化，生物组织都涉及从分子、细胞到宏观尺度上复杂的力生化耦合机理，体现在化学组成、力学性质、几何结构、生物功能等多方面的改变。本项目将在实验基础上，发展生物组织生长发育过程的多尺度、力生化耦合理论，并探究其在癌症发生发展过程中的应用研究。首先，将基于分子生物学和细胞生物学的成果，构建包含多种细胞、细胞外基质等的三维多尺度力学模型与数值模拟方法；其二，基于对机械能、生化能等的能量输运与转化机制的定量描述，发展生物组织生长发育与病变过程的热力学本构理论；其三，研究生物组织在不同条件下力学性质、几何结构和生物功能变化的基本规律与力生物学机制；进而，利用上述理论和方法，探索癌症在诊断和治疗中遇到的几个关键难题。本项目一方面致力于发展力生化耦合的多尺度力学生物学理论模型与计算方法，另一方面为发展相关疾病的诊断和治疗技术提供更为坚实的理论基础。

Biological tissues are complex organizations of cells and extracellular matrices. The development, growth, and pathogenic transformation of biological tissues involve a number of mechano-bio-chemical processes driven by intra- and extracellular changes at molecular, cellular, and tissue levels as well as the intricate interactions between them. It remains a critical problem to elucidate the multiscale coupling between biochemical components, geometric structures, mechanical properties, and biological functions during development and diseases, which would provide invaluable insights to understand the nature of life and design new diagnostic or therapeutic methods. Here, driven by quantitative experiments, we aim to develop multiscale mechano-bio-chemical theories for the development and growth of tissues, with an overall goal to explore their applications in understanding the pathogenesis and progression of diseases such as cancer. Firstly, leveraging current understanding of molecular and cell biology, we will develop a three-dimensional, multiscale mechanical model that incorporates different types of cells and extracellular matrices to simulate the behaviors of biological tissues. Secondly, from the viewpoint of thermodynamics, we will develop a constitutive theory that could describe the dynamics of tissue growth and responses under the conditions of multi-physical fields, by including the conversion between different forms of energies such as chemical and mechanical energies. Thirdly, through combining experiments, theories, and simulations, we will study the evolution of mechanical, architectural, and biological properties under different physiological and pathological conditions, and explore the mechanobiology underneath. Last but not least, we aim to apply the above methods of theoretical analysis and numerical simulations to address a few key challenges in the diagnosis and treatments of high-impact diseases such as cancer. This project will establish novel theories as well as numerical methods for modeling the multiscale mechano-bio-chemical coupling in tissue development, growth, and diseases, providing a foundation for rationally designing and developing novel diagnostic or therapeutic technologies in the future.