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Physical Biology

Josiah D Smith, Leah N Cardwell, David Porciani, Julie A Nguyen, Fabio Gallazzi, Rama Rao Tata, Donald H Burke, Mark A Daniels, Bret Ulery
Peptide amphiphile micelles (PAMs) are attractive vehicles for the delivery of a variety of therapeutic and prophylactic peptides. However, a key limitation of PAMs is their lack of preferential targeting ability. In this paper, we describe our design of a PAM system that incorporates a DNA oligonucleotide amphiphile (antitail amphiphile - AA) to form A/PAMs. A cell-targeting DNA aptamer with a 3' extension sequence (tail) complementary to the AA is annealed to the surface to form aptamer-displaying PAMs (Aptamer~A/PAMs)...
August 20, 2018: Physical Biology
Jamoliddin Razzokov, Saber Naderi, Paul van der Schoot
By means of replica exchange molecular dynamics simulations we investigate how the length of a silk-like, alternating diblock oligopeptide influences its secondary and quaternary structure. We carry out simulations for two protein sizes consisting of three and five blocks, and study the stability of a single protein, a dimer, a trimer and a tetramer. Initial configurations of our simulations are β-roll and β-sheet structures. We find that for the triblock the secondary and quaternary structures upto and including the tetramer are unstable: the proteins melt into random coil structures and the aggregates disassemble either completely or partially...
September 12, 2018: Physical Biology
Hu Jin, Alex I Finnegan, Jun S Song
Nucleosomes form the fundamental building blocks of eukaryotic chromatin, and previous attempts to understand the principles governing their genome-wide distribution have spurred much interest and debate in biology. In particular, the precise role of DNA sequence in shaping local chromatin structure has been controversial. This paper rigorously quantifies the contribution of hitherto-debated sequence features-including G+C content, 10.5 bp periodicity, and poly(dA:dT) tracts-to three distinct aspects of genome-wide nucleosome landscape: occupancy, translational positioning and rotational positioning...
September 12, 2018: Physical Biology
Kharananda Sharma, Bradley J Roth
In the heart, cardiac muscle fibers curve creating zones of membrane forces resulting in regions of mechanotransduction. This study uses the finite difference method to solve the mechanical bidomain equations numerically for a complex fiber geometry. The magnitude of the active tension T is constant but its direction makes an angle with the x-axis that varies with position. Differences between the intracellular and extracellular displacements result from the bidomain behavior of the tissue that gives rise to forces on the integrin proteins in the membrane...
September 12, 2018: Physical Biology
Charles R Doering, Xiaoming Mao, Leonard M Sander
Motile biological cells in tissue often display the phenomenon of durotaxis, i.e. they tend to move towards stiffer parts of substrate tissue. The mechanism for this behavior is not completely understood. We consider simplified models for durotaxis based on the classic persistent random walker scheme. We show that even a one-dimensional model of this type sheds interesting light on the classes of behavior cells might exhibit. Our results strongly indicate that cells must be able to sense the gradient of stiffness in order to show the effects observed in experiment...
September 11, 2018: Physical Biology
Xiaobo Jing, Pavel Loskot, Jin Yu
Transcription plays an essential role in gene expression. The transcription bursting in bacteria has been suggested to be regulated by positive supercoiling accumulation in front of a transcribing RNA polymerase (RNAP) together with gyrase binding on DNA to release the supercoiling. In this work, we study the supercoiling regulation in the case of a battery of RNAPs working together on DNA by constructing a multi-state quantitative model, which allows gradual and stepwise supercoiling accumulation and release in the RNAP transcription...
September 6, 2018: Physical Biology
Lim C Siang, Rodrigo Fernandez-Gonzalez, James J Feng
Germband extension during Drosophila development is primarily driven by cell intercalation, which involves three key components: planar cell polarity, anisotropic myosin contractile forces on cellular junctions, and cellular deformation and movement. Prior experimental work probed each of these factors in depth, but the connection between them remains unclear. This paper presents an integrated chemomechanical model that combines the three factors into a coherent mathematical framework for studying cell intercalation in the germband tissue...
September 6, 2018: Physical Biology
E Piegari, L F Lopez, S Ponce Dawson
The specificity and universality of intracellular [Formula: see text] signals rely on the variety of spatio-temporal patterns that the [Formula: see text] concentration can display. [Formula: see text] liberation through inositol 1,4,5-trisphosphate receptors ([Formula: see text]) is key for this variety. In this paper, we study how the competition between buffers of different kinetics affects [Formula: see text] signals that involve [Formula: see text] release through [Formula: see text]. The study also provides insight into the underlying spatial distribution of the channels that participate in the signals...
August 20, 2018: Physical Biology
Andrew Mugler, Bo Sun
No abstract text is available yet for this article.
August 14, 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...
August 14, 2018: Physical Biology
Ankur H Kulkarni, Aritra Chatterjee, Paturu Kondaiah, Namrata Gundiah
Mechanical properties of cells are shown to regulate cell behaviors leading 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...
August 14, 2018: Physical Biology
Camille Simon, Valentina Caorsi, Clément Campillo, Cécile 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 30, 2018: Physical Biology
Margaret S 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, 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...
July 30, 2018: Physical Biology
Hong-Yan Shih, Harry Mickalide, David T Fraebel, Nigel 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...
July 27, 2018: Physical Biology
Amalie Christensen, Ann-Katrine Vrans West, Lena Wullkopf, Janine Terra Erler, Lene Broeng 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 the experimental data of endothelial and cancer cells. In contrast to the commonly used drag friction, we find that solid friction best captures 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...
July 25, 2018: Physical Biology
Dylan C Young, Jan Scrimgeour
Particle tracking offers significant insight into the molecular mechanics that govern the behavior 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...
July 6, 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
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