Theoretical Studies of Mechanics in Active Matter

该奖项支持物理学和生物学界面上机械可激活性固体的理论研究、推广和教育。在跳动的心脏中，被称为心肌细胞的细胞以一种协调的方式收缩，产生一个从心脏一端穿过到另一端的收缩波前，每次跳动都推动血液通过心脏。成人心脏中的心肌细胞通过涉及离子的电信号刺激其他细胞收缩。然而，在早期胚胎心脏中，PI和合作者认为，由细胞收缩引起的机械应力会给其他细胞发出收缩的信号。因此，胚胎心脏是一种机械可兴奋的固体，其中称为心肌细胞的活性成分对周围组织施加压力，从而激发其他心肌细胞的收缩（从而产生更多的压力）。就像它们简单的表亲——化学可激发系统一样，机械可激发的活性固体可以表现出丰富的行为，比如像心脏收缩波前那样的波前传播，条纹或斑点等图案的形成，或者混沌行为。在这个项目中，PI将研究机械可激发的活性固体的物理学，如胚胎心脏。机械可激发活性固体是一类活性物质——包含许多小成分的系统，例如心肌细胞，它们之间相互作用强烈，并为系统提供能量。活性物质的物理学可能与传统的被动物质的物理学有根本的不同，在传统的被动物质中，单个的微观成分不能提供能量。该奖项支持培养物理学研究生，在他们的研究过程中，将汇集凝聚态物理学许多子领域的思想和技术，并与生物学家密切互动。他们的工作不仅将拓宽物理学中对活性物质的研究，而且将为心脏的工作带来新的视角，并可能导致设计新的合成材料作为活性固体。技术概述：该奖项支持活性物质与生物学界面的理论研究和教育。活性物质是物质的一种形式，通过在微观尺度上注入能量而保持不平衡。一个典型的例子是由运动粒子组成的活跃流体。该项目侧重于可激发活性固体，其成分通过产生应力注入能量。一个例子是跳动的心脏，心肌细胞通过以协调的方式收缩，将能量注入到组织中，形成一个收缩波阵面，每次跳动都穿过心脏泵血。在成人心脏中，收缩波前被理解为化学-电兴奋性问题中的波前传播。来自一个细胞的离子触发下一个细胞释放钙，从而引发细胞收缩。然而，在胚胎心脏中，首席研究员和合作者提出，收缩波前是一种机械兴奋性现象：当细胞收缩时产生应力，有效地扩散到弹性粘性组织中，并触发下一个细胞释放离子导致其收缩。心脏表现出活性物质的反向能量级联特征：通过波前传播的非线性动力学，在细胞尺度上由心肌细胞收缩注入的能量被转导到宏观器官尺度，在那里它导致集体功能-心脏的泵送作用。该理论项目有三个主要目标：(1)对通过应力产生在微观水平注入能量的活性固体进行理论描述；(2)构建与实验观察相一致的心脏机电反应扩散的理论框架，并了解其对心脏发育和进化的影响；(3)更广泛地理解机械反应-扩散系统，使用化学反应-扩散系统的非线性动力学社区发展的理论技术。这里的目的是计算稳态行为和瞬态现象的相图。这样的相位图可能具有表示的区域、波前传播、模式形成、时间振荡或静态行为。该奖项将支持物理学研究生在软物质物理学，机械生物学和生理学的界面工作。在他们的研究过程中，这些学生将汇集凝聚态物理许多子领域的思想和技术，并与生物学家密切互动。他们的工作不仅将拓宽软物质物理学中活性物质的研究，而且将为早期发育和早期进化的心脏带来新的视角，并可能导致设计新的合成材料作为活性固体。

NONTECHNICAL SUMMARYThis award supports theoretical research, outreach and education on mechanically-excitable active solids that lie at the interface of physics and biology. In the beating heart, cells called cardiomyocytes contract in a coordinated fashion to generate a contractile wavefront that crosses from one end of the heart to the other, pushing blood through the heart with each beat. Cardiomyocytes in the adult heart excite other cells to contract using electrical signals involving ions. In the early embryonic heart, however, the PI and collaborators have suggested that the mechanical stress resulting from the contraction of a cell signals other cells to contract. The embryonic heart is therefore a mechanically-excitable solid in which active components called cardiomyocytes exert stresses on surrounding tissue that excite contraction of other cardiomyocytes (and therefore the generation of more stress). Like their simpler cousins, chemically-excitable systems, mechanically-excitable active solids can show rich behavior, such as wavefront propagation as in the contractile wavefront of the heart, the formation of patterns such as stripes or spots, or chaotic behavior. In this project, the PI will investigate the physics of mechanically-excitable active solids such as the embryonic heart.Mechanically-excitable active solids are a class of active matter--systems that contain many small components, for example cardiomyocytes, that interact strongly with each other and that supply energy to the system. The physics of active matter can be fundamentally different from the physics of traditional passive matter, in which individual microscopic components cannot supply energy. This award supports training physics graduate students who, in the course of their research, will bring together ideas and techniques from many subfields of condensed matter physics and interact closely with biologists. Their work will not only broaden the study of active matter within physics, but will bring a new perspective to the workings of the heart and may lead to the design of new synthetic materials as active solids.TECHNICAL SUMMARYThis award supports theoretical research and education on active matter at the interface with biology. Active matter is a form of matter maintained out of equilibrium by energy injected at the microscopic scale. A canonical example is an active fluid of motile particles. This project focuses on excitable active solids, in which constituents inject energy by generating stress. An example is the beating heart, in which cardiomyocyte cells inject energy into the tissue by contracting in a coordinated fashion to create a contractile wavefront that traverses the heart with each beat to pump blood. In the adult heart, the contractile wavefront is understood as wavefront propagation in a chemo-electrical excitability problem. Ions from one cell trigger calcium release in the next cell to initiate its contraction. In the embryonic heart, however, the principal investigator and collaborators proposed that the contractile wavefront is a mechanical excitability phenomenon: stress is generated when a cell contracts, effectively diffuses through elastoviscous tissue, and triggers ion release in the next cell to cause its contraction. The heart exhibits the reverse energy cascade characteristic of active matter: energy injected at the cellular scale by cardiomyocyte contraction is transduced, via the nonlinear dynamics of wavefront propagation, up to the macroscopic organ scale, where it leads to a collective function - the pumping action of the heart.This theoretical project has three main goals: (1) to develop a theoretical description for active solids in which energy is injected at the microscopic level via stress generation; (2) to construct a coherent theoretical framework for mechano-electrical reaction-diffusion in the heart that is consistent with experimental observations, and to understand its implications for development and evolution of the heart; (3) to understand mechanical reaction-diffusion systems more generally, using theoretical techniques developed in the nonlinear dynamics community for chemical reaction-diffusion systems. Here the aim is to calculate phase diagrams for steady-state behavior and transient phenomena. Such a phase diagram might have regions denoted, wavefront propagation, pattern formation, temporal oscillations, or quiescent behavior.This award will support physics graduate students to work at the interface of soft matter physics, mechanobiology and physiology. In the course of their research, these students will bring together ideas and techniques from many subfields of condensed matter physics and interact closely with biologists. Their work will not only broaden the study of active matter within soft matter physics, but will bring a new perspective to early developing and early evolving hearts and may lead to the design of new synthetic materials as active solids.