Efficient energy and information transduction in microscopic nonequilibrium systems

最基本的物理学原理之一指出，无序总是增加，但生物必须维持秩序才能有效地发挥作用。通过不断输入高能分子和输出低能废物，它们远离称为平衡的更无序的状态。 不幸的是，生物系统的物理理论通常假设系统处于平衡状态，主要是因为数学比较简单。但近年来，非平衡理论的重大进展指出，生命系统的一般原则是可能的。这样的理论发展提高了我们对单个分子（例如，蛋白质或DNA分子）抵抗拉伸。然而，这些理论仍然过于简单，无法充分描述更复杂的生物系统和更微妙的干预。 我假设，有效的能源利用和信息处理提供了一个选择性的优势，从而导致一个进化的力量，以改善生物系统中的这些属性。因此，通过对远离平衡的微观模型系统中最佳能量和信息理论效率的理论分析，我将对进化所塑造的生物分子机器的动力学特性做出强有力的、可检验的预测。 为了使这一理论适用于更广泛的生物现象，我将发展非平衡理论，重点是：微观物体不断遇到邻近分子的随机推挤;生物成分与许多其他事物密不可分，必须在这些相互作用中适当地发挥作用，以便良好地发挥作用;以及通过改变细胞中蛋白质的数量来传递信息和能量。这项工作将涉及基础理论，简单模型的探索，复杂系统的更详细的数值计算，并与实验学家密切合作，以测试我们的理论的有效性和实用性。 我的研究计划，涉及我的团队中的几位科学家的培训，将揭示生物系统如何在其面临的操作要求下表现出严格的物理约束，例如当生物系统远离平衡时。这些实验将有助于阐明能量有效的生物功能的基本设计原则。最终，我们可以更好地理解进化的目标及其物理限制。这项工作还将有助于设计新的分子大小的设备，以实现技术目标，如可持续的能量收集，有效的信息存储和操纵，或治疗剂的靶向输送。

One of the most fundamental physical principles states that disorder always increases, yet living things must maintain order to function effectively. Via constant input of high-energy molecules and output of low-energy waste, they stay far from the more disordered state known as equilibrium. Unfortunately, physical theories of biological systems have generally assumed that the system is at equilibrium, mainly because the mathematics is simpler. But in recent years, significant advances in nonequilibrium theory point to the possibility of general principles that characterize living systems. Such theoretical developments have improved our understanding of how a single molecule (e.g., a protein or DNA molecule) resists stretching. The theories are, however, still too simple to adequately describe more complex biological systems and more subtle interventions. I hypothesize that efficient energy usage and information processing provides a selective advantage, thereby leading to an evolutionary force to improve these properties in biological systems. Thus, through theoretical analysis of optimal energetic and information-theoretic efficiency in microscopic model systems far from equilibrium, I will formulate strong and testable predictions about the dynamical properties of biomolecular machines sculpted by evolution. To make this applicable to a wider range of biological phenomena, I will develop nonequilibrium theory that focuses on: the random jostling that microscopic objects constantly encounter from neighboring molecules; the fact that biological components are inextricably connected to many other things and must act appropriately in these interactions in order to function well; and the transduction of information and energy through changing numbers of proteins in a cell. This work will involve fundamental theory, exploration of simple models, more detailed numerical calculations on complex systems, and close collaboration with experimentalists to test the validity and utility of our theories. My research program, involving the training of several scientists in my group, will uncover rigorous physical constraints on how biological systems can behave given the operational imperatives they face, such as when biological systems are driven far from equilibrium. These experiments will help elucidate basic design principles for energetically-efficient biological function. Ultimately, we may obtain a better understanding of the goals of evolution and its physical constraints. This work will also aid the design of new molecular-sized devices to achieve technological goals such as sustainable energy harvesting, efficient information storage and manipulation, or targeted delivery of therapeutic agents.