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Cell Jan 2019Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major... (Review)
Review
Evidence is now mounting that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells. This realization has motivated major efforts to delineate the function of such biomolecular condensates in normal cells and their roles in contexts ranging from development to age-related disease. There is great interest in understanding the underlying biophysical principles and the specific properties of biological condensates with the goal of bringing insights into a wide range of biological processes and systems. The explosion of physiological and pathological contexts involving LLPS requires clear standards for their study. Here, we propose guidelines for rigorous experimental characterization of LLPS processes in vitro and in cells, discuss the caveats of common experimental approaches, and point out experimental and theoretical gaps in the field.
Topics: Cell Physiological Phenomena; Liquid Phase Microextraction; Liquid-Liquid Extraction
PubMed: 30682370
DOI: 10.1016/j.cell.2018.12.035 -
Nature Jan 2010The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an... (Review)
Review
The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.
Topics: Animals; Biomechanical Phenomena; Cell Physiological Phenomena; Cell Shape; Cytoskeleton; Epigenesis, Genetic; Humans
PubMed: 20110992
DOI: 10.1038/nature08908 -
Acta Biochimica Et Biophysica Sinica Nov 2005Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is... (Review)
Review
Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. The progress of apoptosis is regulated in an orderly way by a series of signal cascades under certain circumstances. The caspase-cascade system plays vital roles in the induction, transduction and amplification of intracellular apoptotic signals. Caspases, closely associated with apoptosis, are aspartate-specific cysteine proteases and members of the interleukin-1beta-converting enzyme family. The activation and function of caspases, involved in the delicate caspase-cascade system, are regulated by various kinds of molecules, such as the inhibitor of apoptosis protein, Bcl-2 family proteins, calpain, and Ca2+. Based on the latest research, the members of the caspase family, caspase-cascade system and caspase-regulating molecules involved in apoptosis are reviewed.
Topics: Animals; Apoptosis; Caspases; Cell Physiological Phenomena; Humans; Models, Biological; Signal Transduction
PubMed: 16270150
DOI: 10.1111/j.1745-7270.2005.00108.x -
Physiology (Bethesda, Md.) Oct 2006Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR... (Review)
Review
Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves.
Topics: Animals; Cell Physiological Phenomena; Humans; Protein Biosynthesis; Protein Kinases; Ribosomes; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 16990457
DOI: 10.1152/physiol.00024.2006 -
Annual Review of Biophysics 2015Single-cell techniques have a long history of unveiling fundamental paradigms in biology. Recent improvements in the throughput, resolution, and availability of... (Review)
Review
Single-cell techniques have a long history of unveiling fundamental paradigms in biology. Recent improvements in the throughput, resolution, and availability of microfluidics, computational power, and genetically encoded fluorescence have led to a modern renaissance in microbial physiology. This resurgence in research activity has offered new perspectives on physiological processes such as growth, cell cycle, and cell size of model organisms such as Escherichia coli. We expect these single-cell techniques, coupled with the molecular revolution of biology's recent half-century, to continue illuminating unforeseen processes and patterns in microorganisms, the bedrock of biological science. In this article we review major open questions in single-cell physiology, provide a brief introduction to the techniques for scientists of diverse backgrounds, and highlight some pervasive issues and their solutions.
Topics: Animals; Cell Physiological Phenomena; Escherichia coli; Microfluidics; Single-Cell Analysis
PubMed: 25747591
DOI: 10.1146/annurev-biophys-060414-034236 -
Developmental Cell Oct 2020In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous... (Review)
Review
In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous membraneless organelles assembled via liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartmentalization of cellular functions. Emerging evidence shows that these two organelle types interact in many biological processes. Membranes modulate the biogenesis and dynamics of phase-separated condensates by serving as assembly platforms or by forming direct contacts. Phase separation of membrane-associated proteins participates in various trafficking events, such as clustering of vesicles for temporally controlled fusion and storage, and transport of membraneless condensates on membrane-bound organelles. Phase separation also acts in cargo trafficking pathways by sorting and docking cargos for translocon-mediated transport across membranes, by shuttling cargos through the nuclear pore complex, and by triggering the formation of surrounding autophagosomes for delivery to lysosomes. The coordinated actions of membrane-bound and membraneless organelles ensure spatiotemporal control of various cellular functions.
Topics: Autophagosomes; Biology; Biophysical Phenomena; Cell Physiological Phenomena; Humans; Membranes; Organelles
PubMed: 32726575
DOI: 10.1016/j.devcel.2020.06.033 -
Advances in Physiology Education Dec 2004This brief review is intended to serve as a refresher on the ideas associated with teaching students the physiological basis of the resting membrane potential. The... (Review)
Review
This brief review is intended to serve as a refresher on the ideas associated with teaching students the physiological basis of the resting membrane potential. The presentation is targeted toward first-year medical students, first-year graduate students, or senior undergraduates. The emphasis is on general concepts associated with generation of the electrical potential difference that exists across the plasma membrane of every animal cell. The intention is to provide students a general view of the quantitative relationship that exists between 1) transmembrane gradients for K(+) and Na(+) and 2) the relative channel-mediated permeability of the membrane to these ions.
Topics: Animals; Cell Physiological Phenomena; Electrophysiology; Humans; Membrane Potentials; Physiology
PubMed: 15545342
DOI: 10.1152/advan.00029.2004 -
Genes & Development Dec 2019The idea that liquid-liquid phase separation (LLPS) may be a general mechanism by which molecules in the complex cellular milieu may self-organize has generated much... (Review)
Review
The idea that liquid-liquid phase separation (LLPS) may be a general mechanism by which molecules in the complex cellular milieu may self-organize has generated much excitement and fervor in the cell biology community. While this concept is not new, its rise to preeminence has resulted in renewed interest in the mechanisms that shape and drive diverse cellular self-assembly processes from gene expression to cell division to stress responses. In vitro biochemical data have been instrumental in deriving some of the fundamental principles and molecular grammar by which biological molecules may phase separate, and the molecular basis of these interactions. Definitive evidence is lacking as to whether the same principles apply in the physiological environment inside living cells. In this Perspective, we analyze the evidence supporting phase separation in vivo across multiple cellular processes. We find that the evidence for in vivo LLPS is often phenomenological and inadequate to discriminate between phase separation and other possible mechanisms. Moreover, the causal relationship and functional consequences of LLPS in vivo are even more elusive. We underscore the importance of performing quantitative measurements on proteins in their endogenous state and physiological abundance, as well as make recommendations for experiments that may yield more conclusive results.
Topics: Cell Biology; Cell Physiological Phenomena; Cytological Techniques; Fluorescence Recovery After Photobleaching; Gene Expression Regulation; Liquid-Liquid Extraction; Transcription Factors
PubMed: 31594803
DOI: 10.1101/gad.331520.119 -
ELife Jun 2021Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T...
Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy.
Topics: Animals; Cell Movement; Cell Physiological Phenomena; Cells, Cultured; Collagen; Extracellular Matrix; Female; Immune Checkpoint Inhibitors; Mice; Mice, Inbred C57BL; Neoplasms, Experimental; Programmed Cell Death 1 Receptor; Protein-Lysine 6-Oxidase; T-Lymphocytes; Tumor Microenvironment
PubMed: 34106045
DOI: 10.7554/eLife.58688 -
Current Opinion in Cell Biology Feb 2009
Topics: Biological Evolution; Cell Biology; Cell Physiological Phenomena; Organelles
PubMed: 19185481
DOI: 10.1016/j.ceb.2009.01.010