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Physical Biology

Camille Simon, Valentina Caorsi, Clément Campillo, Cecile Sykes
The ability of mammalian cells to deform their membrane relies on the action of the cytoskeleton. In particular, the dynamics of the actin cytoskeleton, assembling at the plasma membrane, plays a crucial role in controlling cell shape. Many proteins are involved to ensure proper growth of the actin network at the cell membrane. The detailed structure of this network regulates the force that is necessary for membrane deformation. We address here how the presence of capping proteins, which limit the length of actin filaments and thus affects network topology, influences membrane shape...
July 6, 2018: Physical Biology
Amalie Christensen, Ann-Katrine Vransø West, Lena Wullkopf, Janine Erler, Lene B Oddershede, Joachim Mathiesen
Mechanical forces are important factors in the development, coordination and collective motion of cells. Based on a continuum-scale model, we consider the influence of substrate friction on cell motility in confluent living tissue. We test our model on experimental data of endothelial and cancer cells. In contrast to the commonly used drag friction, we find that solid friction captures best the cell speed distribution. From our model, we quantify a number of measurable physical tissue parameters such as the ratio between the viscosity and substrate friction...
June 25, 2018: Physical Biology
Margaret Shun Cheung, Andrei G Gasic
Proteins must fold and function in the immensely complex environment of a cell, i.e. the cytoplasm-this is far from the ideal test-tube setting of a dilute solution. Here we review the advances in protein folding and dynamics inside the cell. In developing principles of protein behavior in vivo, we also begin to understand the organization and dynamics of the cytoplasm as a whole, unifying the single protein scale with the many-protein architectures at the subcellular scale. Our group has significantly contributed to this frontier by characterizing the effect of macromolecular crowding on the distribution of protein conformations...
June 25, 2018: Physical Biology
Ranjit Ranbhor, Anil Kumar, Abhijit Tendulkar, Kirti Patel, Vibin Ramakrishnan, Susheel Durani
Incorporating D amino acids in the protein design alphabet can in principle multiply the design space by many orders of magnitude. All native proteins are polymers composed of L chiral amino acids. Practically limitless in diversity over amino acid sequences, protein structure is limited in folds and thus shapes, principally due to the poly L stereochemistry of their backbone. To diversify shapes, we introduced both L- and D α-amino acids as design alphabets to explore the possibility of generating novel folds, varied in chemical as well as stereo-chemical sequence...
June 20, 2018: Physical Biology
Dylan Christopher Young, Jan Scrimgeour
Particle tracking offers significant insight into the molecular mechanics that govern the behav- ior of living cells. The analysis of molecular trajectories that transition between different motive states, such as diffusive, driven and tethered modes, is of considerable importance, with even single trajectories containing significant amounts of information about a molecule's environment and its interactions with cellular structures. Hidden Markov models (HMM) have been widely adopted to perform the segmentation of such complex tracks...
June 19, 2018: Physical Biology
Estefania Piegari, Lucia Fernanda Lopez, Silvina Ponce Dawson
The specificity and universality of intracellular Ca<sup>2+</sup> signals rely on the variety of spatio-temporal patterns that the Ca<sup>2+</sup> concentration can display. Ca<sup>2+</sup> liberation through inositol 1,4,5-trisphosphate receptors (IP<sub>3</sub>Rs) is key for this variety. In this paper we study how the competition between buffers of different kinetics affects Ca<sup>2+</sup> signals that involve Ca<sup>2+</sup> release through IP<sub>3</sub>Rs...
May 31, 2018: Physical Biology
Hong-Yan Shih, Harry Mickalide, David T Fraebel, Nigel D Goldenfeld, Seppe Kuehn
Phenotypes of individuals in a population of organisms are not fixed. Phenotypic fluctuations, which describe temporal variation of the phenotype of an individual or individual-to-individual variation across a population, are present in populations from microbes to higher animals. Phenotypic fluctuations can provide a basis for adaptation and be the target of selection. Here we present a theoretical and experimental investigation of the fate of phenotypic fluctuations in directed evolution experiments where phenotypes are subject to constraints...
May 15, 2018: Physical Biology
Ankur Kulkarni, Aritra Chatterjee, Paturu Kondaiah, Namrata Gundiah
Mechanical properties of cells regulate cell behaviors which lead to phenotypic changes that may aid in the development and progression of disease. In this study, we used atomic force microscopy (AFM) indentation with a spherical probe to characterize the elastic and viscoelastic properties of invasive (MDA-MB-231) and noninvasive (MCF-7) breast cancer cells treated with transforming growth factor-β (TGF-β). We also used confocal fluorescence imaging to investigate the sub-membrane cytoskeletal structure of the cells...
May 10, 2018: Physical Biology
Bart W Hoogenboom, Mark C Leake
Increasing numbers of physicists engage in research activities that address biological questions from physics perspectives or strive to develop physics insights from active biological processes. The on-going development and success of such activities morph our ways of thinking about what it is to 'do biophysics' and add to our understanding of the physics of life. Many scientists in this research and teaching landscape are homed in physics departments. A challenge for a hosting department is how to group, name and structure such biophysicists to best add value to their emerging research and teaching but also to the portfolio of the whole department...
July 6, 2018: Physical Biology
Tanishq Abraham, Michelle Mao, Cheemeng Tan
Advances in materials engineering have allowed for the development of sophisticated and controlled drug delivery through vesicles. Smart vesicles, capable of sensing single stimulus or multiple stimuli, can be engineered to process specific environmental signals to produce a tailored response. Exhibiting multifunctionality and theranostic abilities, they are a promising platform for new therapeutic methods. Here, we discuss smartness in the context of biosensing vesicles, followed by the various components required to develop a smart vesicle and the design considerations regarding engineering approaches of each...
June 25, 2018: Physical Biology
Anwesha Sarkar, Yuanchang Zhao, Yongliang Wang, Xuefeng Wang
Integrin-transmitted cellular forces are crucial mechanical signals regulating a vast range of cell functions. Although various methods have been developed to visualize and quantify cellular forces at the cell-matrix interface, a method with high performance and low technical barrier is still in demand. Here we developed a force-activatable coating (FAC), which can be simply coated on regular cell culture apparatus' surfaces by physical adsorption, and turn these surfaces to force reporting platforms that enable cellular force mapping directly by fluorescence imaging...
June 25, 2018: Physical Biology
Mohammad Tehrani, Zahra Ghalamzan, Alireza Sarvestani
The classical theory of polymer elasticity is built upon the assumption of network monodispersity-the premise that polymer networks are comprised of sub-chains of equal length. The crosslinking of biopolymers, however, is a random process and the resultant networks are likely to be polydisperse. The effect of structural polydispersity on the mechanical behavior of biopolymer networks is not well understood. The purpose of this contribution is to show how network polydispersity controls mechanical behavior and the ultimate properties of crosslinked semi-flexible filaments at finite deformations...
June 25, 2018: Physical Biology
Marta Marty-Roda, Oda Dahlen, Titus S van Erp, Santiago Cuesta-López
Although previously developed mesoscopic DNA models have successfully reproduced thermodynamic denaturation data, recent studies show that these overestimate the rate of denaturation by orders of magnitude. Using adapted Peyrard-Bishop-Dauxois (PBD) models, we have calculated the denaturation rates of several DNA hairpins and made comparison with experimental data. We show that the addition of a barrier at the onsite potential of the PBD model gives a more accurate description of the unzipping dynamics of short DNA sequences...
June 20, 2018: Physical Biology
L E Wadkin, S Orozco-Fuentes, I Neganova, G Swan, A Laude, M Lako, A Shukurov, N G Parker
We perform a detailed analysis of the migratory motion of human embryonic stem cells in two-dimensions, both when isolated and in close proximity to another cell, recorded with time-lapse microscopic imaging. We show that isolated cells tend to perform an unusual locally anisotropic walk, moving backwards and forwards along a preferred local direction correlated over a timescale of around 50 min and aligned with the axis of the cell elongation. Increasing elongation of the cell shape is associated with increased instantaneous migration speed...
June 13, 2018: Physical Biology
Benedikt von Bronk, Alexandra Götz, Madeleine Opitz
Complex biological systems offer a variety of interesting phenomena at the different physical scales. With increasing abstraction, details of the microscopic scales can often be extrapolated to average or typical macroscopic properties. However, emergent properties and cross-scale interactions can impede naïve abstractions and necessitate comprehensive investigations of these complex systems. In this review paper, we focus on microbial communities, and first, summarize a general hierarchy of relevant scales and description levels to understand these complex systems: (1) genetic networks, (2) single cells, (3) populations, and (4) emergent multi-cellular properties...
June 6, 2018: Physical Biology
Nicholas E Brunk, Lye Siang Lee, James A Glazier, William Butske, Adam Zlotnick
Virus capsids are polymeric protein shells that protect the viral cargo. About half of known virus families have icosahedral capsids that self-assemble from tens to thousands of subunits. Capsid disassembly is critical to the lifecycles of many viruses yet is poorly understood. Here, we apply a graph and percolation theory to examine the effect of removing capsid subunits on capsid stability and fragmentation. Based on the structure of the icosahedral capsid of hepatitis B virus (HBV), we constructed a graph of rhombic subunits arranged with icosahedral symmetry...
June 6, 2018: Physical Biology
Shi Liang Feng, Lü Wen Zhou, Shou Qin Lü, Yan Zhang
Directed movement of eukaryotic cells toward spatiotemporally varied chemotactic stimuli enables rapid intracellular signaling responses. While macroscopic cellular manifestation is shaped by balancing external stimuli strength with finite internal delays, the organizing principles of the underlying molecular mechanisms remain to be clarified. Here, we developed a novel modeling framework based on a simple seesaw mechanism to elucidate how cells repeatedly reverse polarity. As a key feature of the modeling, the bottom module of bidirectional molecular transport is successively controlled by three upstream modules of signal reception, initial signal processing, and Rho GTPase regulation...
May 29, 2018: Physical Biology
Ramakanth Neeli-Venkata, Samuel M D Oliveira, Leonardo Martins, Sofia Startceva, Mohamed Bahrudeen, Jose M Fonseca, Marco Minoia, Andre S Ribeiro
Cell division in Escherichia coli is morphologically symmetric due to, among other things, the ability of these cells to place the Z-ring at midcell. Studies have reported that, at sub-optimal temperatures, this symmetry decreases at the single-cell level, but the causes remain unclear. Using fluorescence microscopy, we observe FtsZ-GFP and DAPI-stained nucleoids to assess the robustness of the symmetry of Z-ring formation and positioning in individual cells under sub-optimal and critical temperatures. We find the Z-ring formation and positioning to be robust at sub-optimal temperatures, as the Z-ring's mean width, density and displacement from midcell maintain similar levels of correlation to one another as at optimal temperatures...
May 18, 2018: Physical Biology
Ramon Grima, Sebastian Sonntag, Filippo Venezia, Stefan Kircher, Robert W Smith, Christian Fleck
Spatial relocalization of proteins is crucial for the correct functioning of living cells. An interesting example of spatial ordering is the light-induced clustering of plant photoreceptor proteins. Upon irradiation by white or red light, the red light-active phytochrome, phytochrome B, enters the nucleus and accumulates in large nuclear bodies (NBs). The underlying physical process of nuclear body formation remains unclear, but phytochrome B is thought to coagulate via a simple protein-protein binding process...
May 18, 2018: Physical Biology
Lisa Weber, William Raymond, Brian Munsky
In quantitative analyses of biological processes, one may use many different scales of models (e.g. spatial or non-spatial, deterministic or stochastic, time-varying or at steady-state) or many different approaches to match models to experimental data (e.g. model fitting or parameter uncertainty/sloppiness quantification with different experiment designs). These different analyses can lead to surprisingly different results, even when applied to the same data and the same model. We use a simplified gene regulation model to illustrate many of these concerns, especially for ODE analyses of deterministic processes, chemical master equation and finite state projection analyses of heterogeneous processes, and stochastic simulations...
May 18, 2018: Physical Biology
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