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The Journal of General Physiology Dec 2018Sobolevsky reflects on his unique scientific upbringing in Russia.
Sobolevsky reflects on his unique scientific upbringing in Russia.
Topics: Biophysics; History, 20th Century; History, 21st Century; Russia; Universities
PubMed: 30459255
DOI: 10.1085/jgp.201812265 -
Current Opinion in Cell Biology Apr 2022The endosomal sorting complex required for transport (ESCRT) machinery evolved early in evolution to sculpt and cut cellular membranes. Consisting of three subcomplexes... (Review)
Review
The endosomal sorting complex required for transport (ESCRT) machinery evolved early in evolution to sculpt and cut cellular membranes. Consisting of three subcomplexes termed ESCRT-I, -II and -III, this machinery is recruited to various cellular locations to perform key steps in essential processes such as protein degradation, cell division, and membrane sealing. Here we review recent discoveries that have shed light on biophysical and molecular mechanisms of ESCRTs in endolysosomal protein degradation and nuclear envelope sealing, and we discuss how dysfunctional ESCRTs can lead to diseases such as cancer and neurodegenerative disorders.
Topics: Biological Transport; Biophysics; Cell Movement; Endosomal Sorting Complexes Required for Transport; Protein Transport
PubMed: 35248976
DOI: 10.1016/j.ceb.2022.01.007 -
Biophysical Journal Jan 2022
Topics: Biophysics
PubMed: 34951952
DOI: 10.1016/j.bpj.2021.12.026 -
International Journal of Molecular... Oct 2021Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years,... (Review)
Review
Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years, calcineurin has been the subject of extensive investigation. Many of its cellular and physiological functions have been described, and the underlying biophysical mechanisms are the subject of active investigation. With the abundance of techniques and experimental designs utilized to study calcineurin and its numerous substrates, it is difficult to reconcile the available information. There have been a plethora of reports describing the role of calcineurin in cardiac disease. However, a physiological role of calcineurin in healthy cardiomyocyte function requires clarification. Here, we review the seminal biophysical and structural details that are responsible for the molecular function and inhibition of calcineurin. We then focus on literature describing the roles of calcineurin in cardiomyocyte physiology and disease.
Topics: Animals; Biophysics; Calcineurin; Heart; Heart Diseases; Humans; Myocytes, Cardiac; Signal Transduction
PubMed: 34768996
DOI: 10.3390/ijms222111565 -
Proceedings of the National Academy of... Mar 2023During the biofilm life cycle, bacteria attach to a surface and then reproduce, forming crowded, growing communities. Many theoretical models of biofilm growth dynamics...
During the biofilm life cycle, bacteria attach to a surface and then reproduce, forming crowded, growing communities. Many theoretical models of biofilm growth dynamics have been proposed; however, difficulties in accurately measuring biofilm height across relevant time and length scales have prevented testing these models, or their biophysical underpinnings, empirically. Using white light interferometry, we measure the heights of microbial colonies with nanometer precision from inoculation to their final equilibrium height, producing a detailed empirical characterization of vertical growth dynamics. We propose a heuristic model for vertical growth dynamics based on basic biophysical processes inside a biofilm: diffusion and consumption of nutrients and growth and decay of the colony. This model captures the vertical growth dynamics from short to long time scales (10 min to 14 d) of diverse microorganisms, including bacteria and fungi.
Topics: Biofilms; Biophysics; Diffusion; Heuristics; Interferometry
PubMed: 36881625
DOI: 10.1073/pnas.2214211120 -
Frontiers in Neural Circuits 2016The intracerebral local field potential (LFP) is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a... (Review)
Review
The intracerebral local field potential (LFP) is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a composite signal that receives contributions from multiple neural sources, yet interpreting its nature and significance may be hindered by several confounding factors and technical limitations. By and large, the main factor defining the amplitude of LFPs is the geometry of the current sources, over and above the degree of synchronization or the properties of the media. As such, similar levels of activity may result in potentials that differ in several orders of magnitude in different populations. The geometry of these sources has been experimentally inaccessible until intracerebral high density recordings enabled the co-activating sources to be revealed. Without this information, it has proven difficult to interpret a century's worth of recordings that used temporal cues alone, such as event or spike related potentials and frequency bands. Meanwhile, a collection of biophysically ill-founded concepts have been considered legitimate, which can now be corrected in the light of recent advances. The relationship of LFPs to their sources is often counterintuitive. For instance, most LFP activity is not local but remote, it may be larger further from rather than close to the source, the polarity does not define its excitatory or inhibitory nature, and the amplitude may increase when source's activity is reduced. As technological developments foster the use of LFPs, the time is now ripe to raise awareness of the need to take into account spatial aspects of these signals and of the errors derived from neglecting to do so.
Topics: Animals; Biophysics; Brain; Electroencephalography; Electrophysiological Phenomena; Humans; Nerve Net; Neurosciences
PubMed: 28018180
DOI: 10.3389/fncir.2016.00101 -
Annual Review of Biophysics May 2019Structural DNA nanotechnology is beginning to emerge as a widely accessible research tool to mechanistically study diverse biophysical processes. Enabled by scaffolded... (Review)
Review
Structural DNA nanotechnology is beginning to emerge as a widely accessible research tool to mechanistically study diverse biophysical processes. Enabled by scaffolded DNA origami in which a long single strand of DNA is weaved throughout an entire target nucleic acid assembly to ensure its proper folding, assemblies of nearly any geometric shape can now be programmed in a fully automatic manner to interface with biology on the 1-100-nm scale. Here, we review the major design and synthesis principles that have enabled the fabrication of a specific subclass of scaffolded DNA origami objects called wireframe assemblies. These objects offer unprecedented control over the nanoscale organization of biomolecules, including biomolecular copy numbers, presentation on convex or concave geometries, and internal versus external functionalization, in addition to stability in physiological buffer. To highlight the power and versatility of this synthetic structural biology approach to probing molecular and cellular biophysics, we feature its application to three leading areas of investigation: light harvesting and nanoscale energy transport, RNA structural biology, and immune receptor signaling, with an outlook toward unique mechanistic insight that may be gained in these areas in the coming decade.
Topics: Biomimetics; Biophysics; DNA; RNA; Receptors, Immunologic; Signal Transduction
PubMed: 31084582
DOI: 10.1146/annurev-biophys-052118-115259 -
Cellular and Molecular Life Sciences :... Dec 2023Cells and tissues display a remarkable range of plasticity and tissue-patterning activities that are emergent of complex signaling dynamics within their... (Review)
Review
Cells and tissues display a remarkable range of plasticity and tissue-patterning activities that are emergent of complex signaling dynamics within their microenvironments. These properties, which when operating normally guide embryogenesis and regeneration, become highly disordered in diseases such as cancer. While morphogens and other molecular factors help determine the shapes of tissues and their patterned cellular organization, the parallel contributions of biophysical control mechanisms must be considered to accurately predict and model important processes such as growth, maturation, injury, repair, and senescence. We now know that mechanical, optical, electric, and electromagnetic signals are integral to cellular plasticity and tissue patterning. Because biophysical modalities underly interactions between cells and their extracellular matrices, including cell cycle, metabolism, migration, and differentiation, their applications as tuning dials for regenerative and anti-cancer therapies are being rapidly exploited. Despite this, the importance of cellular communication through biophysical signaling remains disproportionately underrepresented in the literature. Here, we provide a review of biophysical signaling modalities and known mechanisms that initiate, modulate, or inhibit plasticity and tissue patterning in models of regeneration and cancer. We also discuss current approaches in biomedical engineering that harness biophysical control mechanisms to model, characterize, diagnose, and treat disease states.
Topics: Humans; Neoplasms; Signal Transduction; Bioengineering; Biophysics; Cell Communication; Tumor Microenvironment
PubMed: 38099951
DOI: 10.1007/s00018-023-05054-6 -
ELife Jun 2022Bacteria are ubiquitous in our daily lives, either as motile planktonic cells or as immobilized surface-attached biofilms. These different phenotypic states play key...
Bacteria are ubiquitous in our daily lives, either as motile planktonic cells or as immobilized surface-attached biofilms. These different phenotypic states play key roles in agriculture, environment, industry, and medicine; hence, it is critically important to be able to predict the conditions under which bacteria transition from one state to the other. Unfortunately, these transitions depend on a dizzyingly complex array of factors that are determined by the intrinsic properties of the individual cells as well as those of their surrounding environments, and are thus challenging to describe. To address this issue, here, we develop a generally-applicable biophysical model of the interplay between motility-mediated dispersal and biofilm formation under positive quorum sensing control. Using this model, we establish a universal rule predicting how the onset and extent of biofilm formation depend collectively on cell concentration and motility, nutrient diffusion and consumption, chemotactic sensing, and autoinducer production. Our work thus provides a key step toward quantitatively predicting and controlling biofilm formation in diverse and complex settings.
Topics: Bacteria; Biofilms; Biophysics; Plankton; Quorum Sensing
PubMed: 35642782
DOI: 10.7554/eLife.76380 -
Proceedings of the National Academy of... Jun 2006Helices are among the simplest shapes that are observed in the filamentary and molecular structures of nature. The local mechanical properties of such structures are...
Helices are among the simplest shapes that are observed in the filamentary and molecular structures of nature. The local mechanical properties of such structures are often modeled by a uniform elastic potential energy dependent on bending and twist, which is what we term a rod model. Our first result is to complete the semi-inverse classification, initiated by Kirchhoff, of all infinite, helical equilibria of inextensible, unshearable uniform rods with elastic energies that are a general quadratic function of the flexures and twist. Specifically, we demonstrate that all uniform helical equilibria can be found by means of an explicit planar construction in terms of the intersections of certain circles and hyperbolas. Second, we demonstrate that the same helical centerlines persist as equilibria in the presence of realistic distributed forces modeling nonlocal interactions as those that arise, for example, for charged linear molecules and for filaments of finite thickness exhibiting self-contact. Third, in the absence of any external loading, we demonstrate how to construct explicitly two helical equilibria, precisely one of each handedness, that are the only local energy minimizers subject to a nonconvex constraint of self-avoidance.
Topics: Biophysical Phenomena; Biophysics; Models, Molecular; Molecular Conformation
PubMed: 16769895
DOI: 10.1073/pnas.0508370103