Mechanics of cell growth and division

项目总结/摘要 细胞质是一个拥挤的亚细胞环境，充满了细胞器，蛋白质，核酸 和其他大的高分子，以及水和小分子。细胞的生物过程 在这种环境中的作用仍然知之甚少。细胞质中的大分子被认为 施加有助于细胞质组织、相分离和渗透压的物理力。 细胞密度，即细胞组分如蛋白质和核酸的浓度，是一个重要的参数。 这些大分子拥挤效应的关键预测因素。我们实验室和其他实验室的最新证据显示 密度和大分子拥挤效应不是恒定的，而是在细胞周期中发生变化， 以及在各种生理和疾病状态以及发育期间。然而，人们对 这些变化如何影响细胞生理学和力学。因此，细胞密度和 大分子拥挤代表了细胞生理学关键但未充分研究的方面， 大多数细胞过程。 总的目标是阐明物理和分子基础的机制， 负责细胞生长和分裂的细胞过程：有丝分裂，微管动力学，核大小 控制、染色体移动和细胞壁组装。调查的总体目标是确定 细胞质和核质的生物物理特性如何影响这些不同的细胞过程。 特别是，我们的研究将解决细胞内的渗透压所产生的大分子的行为 抑制微管动力学，使细胞核膨胀，调节有丝分裂纺锤体的力学， 调节染色体运动以进行DNA修复。方法包括创新的活细胞测定， 活细胞的生物物理特性（例如微流变学和定量相位成像）和定量 细胞生物学方法在裂殖酵母粟酒裂殖酵母。 这些研究将为新兴的细胞密度领域奠定基础， 对我们理解细胞生物学的一个基本但未被充分研究的方面。这项工作将大大 影响我们对与生物医学相关的细胞生长和分裂机制的理解， 应用包括癌症、衰老和真菌发病机制。

Project Summary/ Abstract The cytoplasm is a crowded subcellular environment that is packed with organelles, proteins, nucleic acids and other large macromolecules, as well as water and small molecules. How cell biological processes function in this milieu remains poorly understood. Macromolecules present in the cytoplasm are thought to exert physical forces that contribute to cytoplasmic organization, phase separation, and osmotic pressure. Cellular density, which is the concentration of cellular components such as proteins and nucleic acids, is a key predictor of these macromolecular crowding effects. Recent evidence from our lab and others reveals that density and macromolecular crowding effects are not constant but actually change during the cell cycle, as well in various physiological and disease states, and during development. However, little is known about how these changes impact cellular physiology and mechanics. Thus, cellular density and the effects of macromolecular crowding represent critical but understudied aspects of cellular physiology that likely impact most cellular processes. The general goals are to elucidate physical- and molecular- based mechanisms responsible for cellular processes responsible for cell growth and division: mitosis, microtubule dynamics, nuclear size control, chromosome mobility and cell wall assembly. A general thrust of the investigations is to determine how the biophysical properties of the cytoplasm and nucleoplasm impact these diverse cellular processes. In particular, our studies will address how intracellular osmotic pressures generated by macromolecules act to dampen microtubule dynamics, inflate the nucleus, modulate the mechanics of the mitotic spindle, and regulate chromosome motility for DNA repair. Approaches include innovative live cell assays for the biophysical properties of living cells (e.g. microrheology and quantitative phase imaging) and quantitative cell biology approaches in the fission yeast Schizosaccharomyces pombe. These studies will establish a foundation for the emerging field of cellular density and will contribute to our understanding of a fundamental but understudied aspect of cell biology. This work will significantly impact our understanding of mechanisms governing cell growth and division that are relevant for biomedical applications including cancer, aging and fungal pathogenesis.