Thermodynamics of Growing Active and Living Matter

当我们从本科物理/化学中学习经典热力学时，我们经常假设大量的粒子~10^23，平衡和准静态过程。在这个非常严格的限制下，热力学量，如散热Q，可以用教科书公式Q= T\ δ S来计算，其中S是构型熵。然而，在现实生活中，大多数物理过程既不是准静态的，也不是平衡的。此外，在许多生物系统中，自由度的数目也远小于10^23，在这种情况下，热波动变得很重要。因此，热力学的量，如热、功和熵需要被重新定义（随机热力学）。本研究的第一个目的是将随机热力学理论扩展到包括生灭过程，例如活组织和细菌菌落生长中的细胞分裂和凋亡。随机热力学的一个重要应用是生物机器的前景，这些生物机器由一些细菌的游动运动提供动力，甚至是我们体内的细胞分裂和凋亡。例如，我们在实验和理论上都知道，如果我们把一个不对称的齿轮放在一个充满游动细菌的浴缸里，这个齿轮就能以某种方式朝一个方向持续旋转。细菌本身，在没有齿轮的情况下，会以完全随机的方向游动；然而，细菌和不对称齿轮之间的相互作用可以打破时间反转对称性，从而产生宏观的单向电流。虽然这种现象已经在运动活性物质（如游泳细菌）中得到了很好的证实，但对非运动生长活性物质（如活组织和细菌菌落中的细胞分裂和凋亡）知之甚少。在这项研究中，我将探索细胞分裂和凋亡作为生物机器发展的新途径。这一点很重要，因为与细胞运动不同，细胞分裂和凋亡是生物物质的普遍特性。我对这种机器的设计原则将为未来可能在医疗技术和组织工程中的应用铺平道路，例如使用非均匀支架来控制组织的生长。最后，我将研究这些机器的热力学性质。特别是，我将量化生物组织和细菌菌落内出生和死亡过程的信息熵产生，即粒子分裂成两个并消失在其他地方。为了实现这一点，我将扩展目前的随机热力学理论，包括出生和死亡过程以及比准静态（即淬火）快得多的随机过程。这些信息对于理解如何将小尺度（即细胞周期）的时间反转对称性破缺转化为大尺度（即组织和细菌菌落中的集体运动）至关重要。除了对活性/生物物质的明显应用外，我的研究还将有助于改变热力学科学，例如了解淬火过程和/或接近临界点的过程中的能量流，其中热波动很重要。

When we learnt classical thermodynamics from undergraduate physics/chemistry, we often assumed a large number of particles ~10^23, equilibrium, and quasi-static process. In this very restrictive limit, thermodynamic quantities such as heat dissipation Q, can be computed using the textbook formula Q= T\Delta S, where S is the configurational entropy. However, in real lives, most physical processes are neither quasi-static nor equilibrium. Furthermore, in many biological systems, the number of degrees of freedom is also much less than 10^23, and in this regime, thermal fluctuations become important. Thus, thermodynamic quantities such as heat, work and entropy need to be redefined properly (Stochastic Thermodynamics). The first aim of this research is to extend the theory of stochastic thermodynamics to include birth and death process, e.g., cellular division and apoptosis in living tissues and growing bacterial colonies.One important application of stochastic thermodynamics is the prospects of biological machines, which are powered by the swimming motility in some bacteria, or even cellular division and apoptosis in our bodies. For instance, it has been well known experimentally and theoretically that if we place an asymmetric cog inside a bath full of swimming bacteria, the cog can somehow rotate persistently in one direction. The bacteria themselves, in the absence of the cog, swim in a completely random direction; and yet the interaction between the bacteria and the asymmetric cog can break time reversal symmetry to create a macroscopic unidirectional current. Although this phenomenon has been well established in motile active matter (such as swimming bacteria), very little is known about non-motile growing active matter (such as cell division and apoptosis in living tissues and bacterial colonies).In this research, I will explore cellular division and apoptosis as a new route to the development of biological machines. This is important because unlike cell motility, cell division and apoptosis are universal properties of living matter. My design principles for such machines will pave the way for future possible applications in healthcare technologies and tissue engineering, such controlling the growth of tissue using non-uniform scaffolding.Finally, I will investigate the thermodynamic properties of these machines. In particular, I will quantify the informatic entropy production of the birth and death process inside biological tissues and bacterial colonies, i.e., particles dividing into two and disappearing elsewhere. To achieve this, I will extend the current theory of stochastic thermodynamics to include birth and death process and stochastic processes that are much faster than quasi-static (i.e., quenching). This information will be crucial in understanding how time reversal symmetry breaking at small scales (i.e., cell cycle) can be translated into large scales (i.e., collective motion in tissues and bacterial colonies). Apart from obvious applications to active/living matter, my research will also help to transform the science of thermodynamics, such as understanding the energy flow in a quenching process and/or processes close to a critical point, where thermal fluctuations are important.