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Physical Biology

Paul C Bressloff, Hyunjoong Kim
Morphogen protein gradients play an important role in the spatial regulation of patterning during embryonic development. The most commonly accepted mechanism for gradient formation is diffusion from a source combined with degradation. Recently, there has been growing interest in an alternative mechanism, which is based on the direct delivery of morphogens along thin, actin-rich cellular extensions known as cytonemes. In this paper, we develop a bidirectional motor transport model for the flux of morphogens along cytonemes, linking a source cell to a one-dimensional array of target cells...
January 9, 2018: Physical Biology
Monique Tirion, Daniel Ben-Avraham
We have extended our analytically derived PDB-NMA formulation, Atomic Torsional Modal Analysis or ATMAN \cite{tirion14}, to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3\AA~resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50\AA~sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures...
December 18, 2017: Physical Biology
Dandan Chen, Lei Yang, Xinjian Chen, Xihui Zhang, Yongming Liu, Zhengqing Guo, Leshuai W Zhang
The morphology of 2D cell colonies has been studied to understand tumor metastasis in the past decades. However, 2D cell cultures are lack of many features of 3D tissues, and their physiological behaviors are quite different from solid tumors in vivo. In this work, we studied the multi-cellular tumor spheroid (MCTS) spreading on the substrate, which keeps parts of 3D tissue characteristics and facilitates cell tracking through 2D imaging. By using high content imaging system (HCS), we tracked multiple spheroids in one single 96-well plate for 36h...
December 18, 2017: Physical Biology
Yunsong Zhang, Jingchen Feng, Shay I Heizler, Herbert Levine
How cells move through the three-dimensional extracellular matrix (ECM) is of increasing interest in attempts to understand important biological processes such as cancer metastasis. Just as in motion on flat surfaces, it is expected that experimental measurements of cell-generated forces will provide valuable information for uncovering the mechanisms of cell migration. However, the recovery of forces in fibrous biopolymer networks may suffer from large errors. Here, within the framework of lattice-based models, we explore possible issues in force recovery by solving the inverse problem: how can one determine the forces cells exert to their surroundings from the deformation of the ECM? Our results indicate that irregular cell traction patterns, the uncertainty of local fiber stiffness, the non-affine nature of ECM deformations and inadequate knowledge of network topology will all prevent the precise force determination...
December 12, 2017: Physical Biology
Bozhi Tian, John A Rogers, Peidong Yang, Zhenan Bao, Nicholas A Melosh, Alon Gorodetsky, Timothy Lu, Polina Anikeeva, Michal Cifra, Stefano Cestellos-Blanco, Joao Carvalho-de-Souza, Francisco Bezanilla, Jia Liu, Martin Hjort, Yuhong Cao, Guglielmo Lanzani, Fabio Benfenati, Giulia Galli, Francois Gygi, Rylan Kautz, Samuel Sungil Kim, Ondrej Krivosudský, Daniel Havelka, Yuanwen Jiang, Shuai Xu
This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world...
December 5, 2017: Physical Biology
Kiyoshi Mizuuchi, Anthony G Vecchiarelli
The MinD and MinE proteins of Escherichia coli self-organize into a standing-wave oscillator on the membrane to help align division at mid-cell. When unleashed from cellular confines, MinD and MinE form a spectrum of patterns on artificial bilayers - static amoebas, traveling waves, traveling mushrooms, and bursts with standing-wave dynamics. We recently focused our cell-free studies on bursts because their dynamics recapitulate many features of Min oscillation observed in vivo. The data unveiled a patterning mechanism largely governed by MinE regulation of MinD interaction with membrane...
November 30, 2017: Physical Biology
Nadia Goncalves, Sofia Startceva, Cristina Palma, Mohamed Bahrudeen, Samuel Oliveira, Andre Sanches Ribeiro
From in vivo single-cell, single-RNA measurements of the activation times and subsequent steady-state active transcription kinetics of a single-copy Lac-ara-1 promoter in Escherichia coli, we characterize the intake kinetics of the inducer (IPTG) from the media, following temperature shifts. For this, for temperature shifts of various degrees, we obtain the distributions of transcription activation times as well as the distributions of intervals between consecutive RNA productions following activation in individual cells...
November 28, 2017: Physical Biology
Yasemin Bozkurt Varolgunes, Alper Demir
It is widely believed that the interactions of proteins with ligands and other proteins are determined by their dynamic characteristics as opposed to only static, time-invariant processes. We propose a novel computational technique, called ProteinAC (PAC), that can be used to analyze small scale functional protein motions as well as interactions with ligands directly in the frequency domain. PAC was inspired by a frequency domain analysis technique that is widely used in electronic circuit design, and can be applied to both coarse-grained and all-atom models...
November 28, 2017: Physical Biology
Karen Castillo, Ignacio Diaz-Franulic, Jonathan Canan, Fernando Gonzalez-Nilo, Ramon Latorre
Temperature sensing is one of the most ancient capabilities of living organisms and is essential to sustain life, because failures in avoiding extreme noxious temperatures can result in tissue damage or death. A subset of members of the transient receptor potential (TRP) ion channel family is finely tuned to detect temperatures ranging from extreme cold to noxious heat, giving rise to thermoTRP channels. Structural and functional experiments have shown that thermoTRP channels are allosteric proteins, containing different domains that sense changes in temperature, among other stimuli, triggering pore opening...
November 14, 2017: Physical Biology
Ramakrishnan Natesan, K K Sreeja, Arpita Roychoudhuri, David M Eckmann, Portonovo S Ayyaswamy, Tobias Baumgart, Thomas Pucadyil, Shivprasad Vitthal Patil, Valerie M Weaver, Ravi Radhakrishnan
Thermal fluctuations in cell membranes manifest as an excess area (Aex) which governs a multitude of physical process at the sub-micron scale. We present a theoretical framework, based on an in silico tether pulling method, which may be used to reliably estimate Aex in live cells. We perform our simulations in two different thermodynamic ensembles: (i) the constant projected area and (ii) the constant frame tension ensembles and show the equivalence of our results in the two. The tether forces estimated from our simulations compare well with our experimental measurements for tethers extracted from ruptured GUVs and HeLa cells...
November 8, 2017: Physical Biology
Michael Robert Mitchell, Stanislas Leibler
The abundance of available protein static structural data makes more effective analysis and interpretation of this data a valuable tool to supplement experimental study of protein mechanics. Structural displacements can be difficult to analyze and interpret. Previously, we showed that strains provide a more natural and interpretable representation of protein deformations, revealing mechanical coupling between spatially distinct sites of allosteric proteins. Here, we demonstrate that other transformations of displacements yield additional insights...
November 8, 2017: Physical Biology
Sagardip Majumder, Allen P Liu
Engineering artificial cells to mimic one or multiple fundamental cell biological functions is an emerging area of synthetic biology. Reconstituting functional modules from biological components in vitro is a challenging yet an important essence of bottom-up synthetic biology. Here we describe the concept of building artificial platelets using bottom-up synthetic biology and the four functional modules that together could enable such an ambitious effort.
November 1, 2017: Physical Biology
Luke Coburn, Hender Lopez, Irin-Maya Schouwenaar, Alpha Yap, Vladimir Lobaskin, Guillermo Gomez
Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood...
November 1, 2017: Physical Biology
Darryl C W Foo, Eugene Terentjev
We analyse a role of cooperative interaction between neighbouring adhesion-mechanosensor complexes by constructing an Ising-like Hamiltonian describing the free energy of cell adhesion on a substrate as a lattice of 3-state mechanosensing sites involving focal adhesion kinase (FAK). We use Monte Carlo stochastic algorithm to find equilibrium configurations of these mechanosensors in two representative geometries: on a 1D ring representing the rim of a cell on flat surface, and a 2D bounded surface representing the whole area of cell contact with flat surface...
October 23, 2017: Physical Biology
Sai Teja Pusuluri, Alex H Lang, Pankaj Mehta, Horacio E Castillo
Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used...
December 6, 2017: Physical Biology
Khanh N Dinh, Roger B Sidje
Monte Carlo methods such as the stochastic simulation algorithm (SSA) have traditionally been employed in gene regulation problems. However, there has been increasing interest to directly obtain the probability distribution of the molecules involved by solving the chemical master equation (CME). This requires addressing the curse of dimensionality that is inherent in most gene regulation problems. The finite state projection (FSP) seeks to address the challenge and there have been variants that further reduce the size of the projection or that accelerate the resulting matrix exponential...
November 3, 2017: Physical Biology
Ahmet Gul, Burak Erman
Prediction of peptide binding on specific human leukocyte antigens (HLA) has long been studied with successful results. We herein describe the effects of entropy and dynamics by investigating the binding stabilities of 10 nanopeptides on various HLA Class I alleles using a theoretical model based on molecular dynamics simulations. The fluctuational entropies of the peptides are estimated over a temperature range of 310-460 K. The estimated entropies correlate well with experimental binding affinities of the peptides: Peptides that have higher binding affinities have lower entropies compared to non-binders, which have significantly larger entropies...
October 16, 2017: Physical Biology
Lionel Uhl, Sam Dukan, Audrey Dumont
Almost all living organisms use protein chaperones with a view to preventing proteins from misfolding or aggregation either spontaneously or during cellular stress. This work uses a reaction-diffusion stochastic model to describe the dynamic localization of the Hsp70 chaperone DnaK in E. coli cells during transient proteotoxic collapse characterized by the accumulation of insoluble proteins. In the model, misfolded ("abnormal") proteins are produced during alcoholic stress and have the propensity to aggregate with a polymerization like kinetics...
October 5, 2017: Physical Biology
Sai Teja Pusuluri, Alex H Lang, Pankaj Mehta, Horacio Castillo
Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an open problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple one-dimensional reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used...
October 4, 2017: Physical Biology
Evelyne Kolb, Valérie Legue, Marie-Béatrice Bogeat-Triboulot
Plant root system development is highly modulated by the physical properties of the soil and especially by its mechanical resistance to penetration. The interplay between the mechanical stresses exerted by the soil and root growth is of particular interest for many communities, in agronomy and soil science as well as in biomechanics and plant morphogenesis. In contrast to shoots, roots apices must exert a growth pressure to penetrate strong soils and reorient their growth trajectory to cope with obstacles like stones or hardpans or to follow the tortuous paths of the soil porosity...
October 4, 2017: Physical Biology
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