Mechanics of cell growth and division

细胞生长和分裂的机制

• 批准号: 10642925
• 负责人: Fred Chang
• 金额: $ 56.53万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642925
• 关键词: Aging; Biological Process; Cell Cycle; Cell Nucleus; Cell Wall; Cell division; Cell physiology; Cells; Cellular Assay; Cellular biology; Chromosomes; Collection; Crowding; Cytoplasm; Cytoskeleton; DNA Repair; Development; Disease; Environment; Fission Yeast; Foundations; Goals; Image; Investigation; Life; Malignant Neoplasms; Mechanics; Microtubules; Mitosis; Mitotic spindle; Molecular; Nuclear; Nucleic Acids; Nucleoplasm; Organelles; Osmotic Pressure; Pathogenesis; Phase; Physiological; Process; Proteins; Rheology; Water; Work; biophysical properties; cell growth; cell motility; density; innovation; macromolecule; molecular dynamics; small molecule

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.

项目概要/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 和其他大分子，以及水和小分子。细胞的生物过程如何 人们对这种环境中的功能仍然知之甚少。细胞质中存在的大分子被认为 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，即蛋白质和核酸等细胞成分的浓度，是 这些大分子拥挤效应的关键预测因子。我们实验室和其他实验室的最新证据表明 密度和大分子拥挤效应不是恒定的，而是在细胞周期中实际上发生变化， 以及各种生理和疾病状态以及发育过程中。然而，人们对此知之甚少 这些变化如何影响细胞生理学和力学。因此，细胞密度和影响 大分子拥挤代表了细胞生理学的关键但尚未充分研究的方面，可能会影响 大多数细胞过程。 总体目标是阐明基于物理和分子的机制 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、染色体迁移性和细胞壁组装。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，我们的研究将解决大分子产生的细胞内渗透压如何发挥作用 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，以及 调节DNA修复的染色体运动。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 裂殖酵母裂殖酵母的细胞生物学方法。 这些研究将为新兴的细胞密度领域奠定基础，并将有助于 帮助我们了解细胞生物学的一个基本但尚未得到充分研究的方面。这项工作将显着 影响我们对生物医学相关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。