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Physical Biology

Rob Johnson, Brian Munsky
Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity...
April 21, 2017: Physical Biology
Isabell Weber, Seok-Hyun Yun, Guillano Scarcelli, Kristian Franze
Cells in the central nervous system (CNS) respond to the stiffness of their environment. CNS tissue is mechanically highly heterogeneous, thus providing motile cells with region-specific mechanical signals. While CNS mechanics has been measured with a variety of techniques, reported values of tissue stiffness vary greatly, and the morphological structures underlying spatial changes in tissue stiffness remain poorly understood. We here exploited two complementary techniques, contact-based atomic force microscopy and contact-free Brillouin microscopy, to determine the mechanical properties of ruminant retinae, which are built up by different tissue layers...
April 13, 2017: Physical Biology
Josephine Lembong, Benedikt Sabass, Howard Stone
The maintenance of tissue integrity is essential for the life of multicellular organisms. Healing of a skin wound is a paradigm for how various cell types localize and repair tissue perturbations in an orchestrated fashion. To investigate biophysical mechanisms associated with wound localization, we focus on a model system consisting of a fibroblast monolayer on an elastic substrate. We find that the creation of an edge in the monolayer causes cytosolic calcium oscillations throughout the monolayer. The oscillation frequency increases with cell density, which shows that wound-induced calcium oscillations occur collectively...
April 5, 2017: Physical Biology
Hamid Teimouri, Elgin Korkmazhan, Joel Stavans, Erel Levine
Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA...
March 28, 2017: Physical Biology
David Pincus, Orna Resnekov, Kimberly Reynolds
Allosteric regulation provides a way to control protein activity at the time scale of milliseconds to seconds inside the cell. An ability to engineer synthetic allosteric systems would be of practical utility for the development of novel biosensors, creation of synthetic cell signaling pathways, and design of small molecule pharmaceuticals with regulatory impact. To this end, we outline a general approach - termed Rational Engineering of Allostery at Conserved Hotspots (REACH) - to introduce novel regulation into a protein of interest by exploiting latent allostery that has been hard-wired by evolution into its structure...
March 6, 2017: Physical Biology
Bartolome Sabater, Dolores Marin
Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 34 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle on the function of the Warburg effect. Productions of free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) per mole linearly vary with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0...
March 6, 2017: Physical Biology
Thomas Blasi, Florian Buettner, Michael Strasser, Carsten Marr, Fabian Theis
MOTIVATION: Accessing gene expression at the single cell level has unraveled often large heterogeneity among seemingly homogeneous cells, which remained obscured in traditional population based approaches. The computational analysis of single-cell transcriptomics data, however, still imposes unresolved challenges with respect to normalization, visualization and modeling the data. One such issue are differences in cell size, which introduce additional variability into the data, for which appropriate normalization techniques are needed...
February 15, 2017: Physical Biology
Alexander Krah, Ulrich Zachariae
Bacteria have developed a variety of different mechanisms to defend themselves from compounds that are toxic to them, such as antibiotics. One of these defence mechanisms is the expulsion of drugs or other noxious compounds by multidrug efflux pumps. Multidrug and toxic compound extrusion (MATE) transporters are efflux pumps that extrude metabolic waste and a variety of antibiotics out of the cell, using an ion gradient as energy source. They function via an alternative-access mechanism. When ions bind in the outward facing conformation, a large conformational change to the inward facing conformation is induced, from which the ion is released and the extruded chemical compound is bound...
February 7, 2017: Physical Biology
R M Noest, Z Jane Wang
Tiger beetles pursue prey by adjusting their heading according to a time-delayed proportional control law that minimizes the error angle (Haselsteiner et al 2014 J. R. Soc. Interface 11 20140216). This control law can be further interpreted in terms of mechanical actuation: to catch prey, tiger beetles exert a sideways force by biasing their tripod gait in proportion to the error angle measured half a stride earlier. The proportional gain was found to be nearly optimal in the sense that it minimizes the time to point directly toward the prey...
April 20, 2017: Physical Biology
Eleanor C Ory, Lekhana Bhandary, Amanda E Boggs, Kristi R Chakrabarti, Joshua Parker, Wolfgang Losert, Stuart S Martin
The periphery of epithelial cells is shaped by opposing cytoskeletal physical forces generated predominately by two dynamic force generating systems-growing microtubule ends push against the boundary from the cell center, and the actin cortex contracts the attached plasma membrane. Here we investigate how changes to the structure and dynamics of the actin cortex alter the dynamics of microtubules. Current drugs target actin polymerization and contraction to reduce cell division and invasiveness; however, the impacts on microtubule dynamics remain incompletely understood...
April 20, 2017: Physical Biology
A V Paraskevov, D K Zendrikov
We show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks...
March 23, 2017: Physical Biology
Kien Nguyen, Paul Charles Whitford
For decades, protein folding and functional dynamics have been described in terms of diffusive motion across an underlying energy landscape. With continued advances in structural biology and high-performance computing, the field is positioned to extend these approaches to large biomolecular assemblies. Through the application of energy landscape techniques to the ribosome, one may work towards establishing a comprehensive description of the dynamics, which will bridge theoretical concepts and experimental observations...
March 22, 2017: Physical Biology
Eric E Keaveny, André E X Brown
A basic issue in the physics of behaviour is the mechanical relationship between an animal and its surroundings. The model nematode C. elegans provides an excellent platform to explore this relationship due to its anatomical simplicity. Nonetheless, the physics of nematode crawling, in which the worm undulates its body to move on a wet surface, is not completely understood and the mathematical models often used to describe this phenomenon are empirical. We confirm that linear resistive force theory, one such empirical model, is effective at predicting a worm's path from its sequence of body postures for forward crawling, reversing, and turning and for a broad range of different behavioural phenotypes observed in mutant worms...
March 22, 2017: Physical Biology
Peeyush Sahay, Pradeep K Shukla, Hemendra M Ghimire, Huda M Almabadi, Vibha Tripathi, Samarendra K Mohanty, Radhakrishna Rao, Prabhakar Pradhan
Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging...
March 1, 2017: Physical Biology
M Schenkelberger, S Shanak, M Finkler, E G Worst, V Noireaux, V Helms, A Ott
Cytosine methylation plays an important role in the epigenetic regulation of eukaryotic gene expression. The methyl-CpG binding domain (MBD) is common to a family of eukaryotic transcriptional regulators. How MBD, a stretch of about 80 amino acids, recognizes CpGs in a methylation dependent manner, and as a function of sequence, is only partly understood. Here we show, using an Escherichia coli cell-free expression system, that MBD from the human transcriptional regulator MeCP2 performs as a specific, methylation-dependent repressor in conjunction with the BDNF (brain-derived neurotrophic factor) promoter sequence...
March 1, 2017: Physical Biology
Michal Wlodarski, Bianca Raciti, Jurij Kotar, Marco Cosentino Lagomarsino, Gillian M Fraser, Pietro Cicuta
While the action of many antimicrobial drugs is well understood at the molecular level, a systems-level physiological response to antibiotics remains largely unexplored. This work considers fluctuation dynamics of both the chromosome and cytosol in Escherichia coli, and their response to sublethal treatments of a clinically important antibiotic, rifampicin. We precisely quantify the changes in dynamics of chromosomal loci and cytosolic aggregates (a rheovirus nonstructural protein known as μNS-GFP), measuring short time-scale displacements across several hours of drug exposure...
February 16, 2017: Physical Biology
Ugne Klibaite, Gordon J Berman, Jessica Cande, David L Stern, Joshua W Shaevitz
Behaviors involving the interaction of multiple individuals are complex and frequently crucial for an animal's survival. These interactions, ranging across sensory modalities, length scales, and time scales, are often subtle and difficult to characterize. Contextual effects on the frequency of behaviors become even more difficult to quantify when physical interaction between animals interferes with conventional data analysis, e.g. due to visual occlusion. We introduce a method for quantifying behavior in fruit fly interaction that combines high-throughput video acquisition and tracking of individuals with recent unsupervised methods for capturing an animal's entire behavioral repertoire...
February 16, 2017: Physical Biology
M S Zamil, A Geitmann
In plant tissues, cells are glued to each other by a pectic polysaccharide rich material known as middle lamella (ML). Along with many biological functions, the ML plays a crucial role in maintaining the structural integrity of plant tissues and organs, as it prevents the cells from separating or sliding against each other. The macromolecular organization and the material properties of the ML are different from those of the adjacent primary cell walls that envelop all plant cells and provide them with a stiff casing...
February 16, 2017: Physical Biology
Xiaona Fang, Jin Wang
Cellular networks have been the focus of studies in modern systems biology. They are crucial in understanding cell functions and related diseases. We review some past progress in both the theory and experiments, and we also provide several future perspectives for the field.
February 16, 2017: Physical Biology
L Shahriyari, A Mahdipour-Shirayeh
Studying the stem cell (SC) niche architecture is a crucial step for investigating the process of oncogenesis and obtaining an effective stem cell therapy for various cancers. Recently, it has been observed that there are two groups of SCs in the SC niche collaborating with each other to maintain tissue homeostasis: border stem cells (BSCs), which are responsible in controlling the number of non-stem cells as well as stem cells, and central stem cells (CeSCs), which regulate the SC niche. Here, we develop a bi-compartmental stochastic model for the SC niche to study the spread of mutants within the niche...
February 16, 2017: Physical Biology
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