Physical biology最新文献

{"title":"Quantum biology. π–π entanglement signatures in protein-DNA interactions","authors":"M. D’Acunto","doi":"10.1088/1478-3975/ac5bda","DOIUrl":"https://doi.org/10.1088/1478-3975/ac5bda","url":null,"abstract":"The biological functions of DNA are carried out by individual proteins that interact with specific sequences along the DNA in order to prime the molecular processes required by the cellular metabolism. Protein-DNA interactions include DNA replication, gene expression and its regulation, DNA repair, DNA restriction and modification by endonucleases, generally classified as enzymatic functions, or transcription factors functions. To find specific binding target sequences and achieve their aims, in less than one second proteins operate in symbiosis with a crowded cellular environment, identifying extremely small cognate sequences along the DNA chain, which range from 15–20 bps for repressors to 4–6 bps for restriction enzymes. In a previous work, we proposed that the extraordinary ability of proteins to identify consensus sequences on DNA in a short time appears to be dependent on specific quantum signatures such as the entanglement of π–π electrons between DNA nucleotides and protein amino acids, where the couple of π electrons function as a radical pair, one π electron is located on a specific site of sequence to be identified and the other one performs a quantum walk to identify possible sites of consensus sequence. In this paper, we use the restriction endonucleases enzymes, EcoRV and EcoRI as a case study. These enzymes are able to recognize 3′-GATACT-5′ or 3′-GAATCT-5′ sequences, respectively. We exploit the analogy of a coin operator with a Bloch sphere to demonstrate that the entanglement between π–π electrons generated at the contacts on specific GA dimers between proteins and DNA relies on the spin of the electrons that form an initial singlet state. The latter is a maximally entangled state so that the identification of specific nucleotides is associated with the formation of singlet states. On the other hand, during the identification of subsequent GA dimers, the spin–orbit interaction on walking π electron induces triplet transitions so that singlet–triplet transitions should manifest an experimentally measurable effect. We propose that the possible experimental evidence of entanglement between π–π electrons may be due to the phosphorescence signal correspondence to triplet decay processes.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49668989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gaussian network model revisited: effects of mutation and ligand binding on protein behavior.","authors":"Burak Erman","doi":"10.1088/1478-3975/ac50ba","DOIUrl":"https://doi.org/10.1088/1478-3975/ac50ba","url":null,"abstract":"<p><p>The coarse-grained Gaussian network model (GNM), considers only the alpha carbons of the folded protein. Therefore it is not directly applicable to the study of mutation or ligand binding problems where atomic detail is required. This shortcoming is improved by including all atom pairs within the coordination shell of each other into the Kirchoff adjacency matrix. Counting all contacts rather than only alpha carbon contacts diminishes the magnitude of fluctuations in the system. But more importantly, it changes the graph-like connectivity structure, i.e., the Kirchoff adjacency matrix of the protein. This change depends on amino acid type which introduces amino acid specific and position specific information into the classical coarse-grained GNM which was originally modeled in analogy with the phantom network model of rubber elasticity. With this modification, it is now possible to explain the consequences of mutation and ligand binding on residue fluctuations, their pair-correlations and mutual information shared by each pair. We refer to the new model as 'all-atom GNM'. Using examples from published data we show that the all-atom GNM gives<i>B</i>-factors that are in better agreement with experiment, can explain effects of mutation on long range communication in PDZ domains and can predict effects of GDP and GTP binding on the dimerization of KRAS.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39879087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal chemotherapy counteracts cancer adaptive resistance in a cell-based, spatially-extended, evolutionary model.","authors":"Matteo Italia,&nbsp;Fabio Dercole,&nbsp;Roberto Lucchetti","doi":"10.1088/1478-3975/ac509c","DOIUrl":"https://doi.org/10.1088/1478-3975/ac509c","url":null,"abstract":"<p><p>Most aggressive cancers are incurable due to their fast evolution of drug resistance. We model cancer growth and adaptive response in a simplified cell-based (CB) setting, assuming a genetic resistance to two chemotherapeutic drugs. We show that optimal administration protocols can steer cells resistance and turned it into a weakness for the disease. Our work extends the population-based model proposed by Orlando<i>et al</i>(2012<i>Phys. Biol.</i>), in which a homogeneous population of cancer cells evolves according to a fitness landscape. The landscape models three types of trade-offs, differing on whether the cells are more, less, or equal effective when generalizing resistance to two drugs as opposed to specializing to a single one. The CB framework allows us to include genetic heterogeneity, spatial competition, and drugs diffusion, as well as realistic administration protocols. By calibrating our model on Orlando<i>et al</i>'s assumptions, we show that dynamical protocols that alternate the two drugs minimize the cancer size at the end of (or at mid-points during) treatment. These results significantly differ from those obtained with the homogeneous model-suggesting static protocols under the pro-generalizing and neutral allocation trade-offs-highlighting the important role of spatial and genetic heterogeneities. Our work is the first attempt to search for optimal treatments in a CB setting, a step forward toward realistic clinical applications.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking the stochastic growth of bacterial populations in microfluidic droplets.","authors":"Daniel Taylor, Nia Verdon, Peter Lomax, Rosalind J Allen, Simon Titmuss","doi":"10.1088/1478-3975/ac4c9b","DOIUrl":"10.1088/1478-3975/ac4c9b","url":null,"abstract":"<p><p>Bacterial growth in microfluidic droplets is relevant in biotechnology, in microbial ecology, and in understanding stochastic population dynamics in small populations. However, it has proved challenging to automate measurement of absolute bacterial numbers within droplets, forcing the use of proxy measures for population size. Here we present a microfluidic device and imaging protocol that allows high-resolution imaging of thousands of droplets, such that individual bacteria stay in the focal plane and can be counted automatically. Using this approach, we track the stochastic growth of hundreds of replicate<i>Escherichia coli</i>populations within droplets. We find that, for early times, the statistics of the growth trajectories obey the predictions of the Bellman-Harris model, in which there is no inheritance of division time. Our approach should allow further testing of models for stochastic growth dynamics, as well as contributing to broader applications of droplet-based bacterial culture.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613235/pdf/EMS151804.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39920371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoskeletal proteins: lessons learned from bacteria.","authors":"Félix Ramos-León,&nbsp;Kumaran S Ramamurthi","doi":"10.1088/1478-3975/ac4ef0","DOIUrl":"https://doi.org/10.1088/1478-3975/ac4ef0","url":null,"abstract":"<p><p>Cytoskeletal proteins are classified as a group that is defined functionally, whose members are capable of polymerizing into higher order structures, either dynamically or statically, to perform structural roles during a variety of cellular processes. In eukaryotes, the most well-studied cytoskeletal proteins are actin, tubulin, and intermediate filaments, and are essential for cell shape and movement, chromosome segregation, and intracellular cargo transport. Prokaryotes often harbor homologs of these proteins, but in bacterial cells, these homologs are usually not employed in roles that can be strictly defined as 'cytoskeletal'. However, several bacteria encode other proteins capable of polymerizing which, although they do not appear to have a eukaryotic counterpart, nonetheless appear to perform a more traditional 'cytoskeletal' function. In this review, we discuss recent reports that cover the structures and functions of prokaryotic proteins that are broadly termed as cytoskeletal, either by sequence homology or by function, to highlight how the enzymatic properties of traditionally studied cytoskeletal proteins may be used for other types of cellular functions; and to demonstrate how truly 'cytoskeletal' functions may be performed by uniquely bacterial proteins that do not display homology to eukaryotic proteins.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39862367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical and biochemical attributes of hybrid epithelial/mesenchymal phenotypes.","authors":"Ayalur Raghu Subbalakshmi,&nbsp;Bazella Ashraf,&nbsp;Mohit Kumar Jolly","doi":"10.1088/1478-3975/ac482c","DOIUrl":"https://doi.org/10.1088/1478-3975/ac482c","url":null,"abstract":"<p><p>The epithelial-mesenchymal transition (EMT) is a biological phenomenon associated with explicit phenotypic and molecular changes in cellular traits. Unlike the earlier-held popular belief of it being a binary process, EMT is now thought of as a landscape including diverse hybrid E/M phenotypes manifested by varying degrees of the transition. These hybrid cells can co-express both epithelial and mesenchymal markers and/or functional traits, and can possess the property of collective cell migration, enhanced tumor-initiating ability, and immune/targeted therapy-evasive features, all of which are often associated with worse patient outcomes. These characteristics of the hybrid E/M cells have led to a surge in studies that map their biophysical and biochemical hallmarks that can be helpful in exploiting their therapeutic vulnerabilities. This review discusses recent advances made in investigating hybrid E/M phenotype(s) from diverse biophysical and biochemical aspects by integrating live cell-imaging, cellular morphology quantification and mathematical modeling, and highlights a set of questions that remain unanswered about the dynamics of hybrid E/M states.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39899776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A physics perspective on collective animal behavior.","authors":"Nicholas T Ouellette","doi":"10.1088/1478-3975/ac4bef","DOIUrl":"https://doi.org/10.1088/1478-3975/ac4bef","url":null,"abstract":"<p><p>The dynamic patterns and coordinated motion displayed by groups of social animals are a beautiful example of self-organization in natural far-from-equilibrium systems. Recent advances in active-matter physics have enticed physicists to begin to consider how their results can be extended from microscale physical or biological systems to groups of real, macroscopic animals. At the same time, advances in measurement technology have led to the increasing availability of high-quality empirical data for the behavior of animal groups both in the laboratory and in the wild. In this review, I survey this available data and the ways that it has been analyzed. I then describe how physicists have approached synthesizing, modeling, and interpreting this information, both at the level of individual animals and at the group scale. In particular, I focus on the kinds of analogies that physicists have made between animal groups and more traditional areas of physics.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39941474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of cell-matrix interactions in connective tissue mechanics.","authors":"Iain Muntz,&nbsp;Michele Fenu,&nbsp;Gerjo J V M van Osch,&nbsp;Gijsje H Koenderink","doi":"10.1088/1478-3975/ac42b8","DOIUrl":"https://doi.org/10.1088/1478-3975/ac42b8","url":null,"abstract":"<p><p>Living tissue is able to withstand large stresses in everyday life, yet it also actively adapts to dynamic loads. This remarkable mechanical behaviour emerges from the interplay between living cells and their non-living extracellular environment. Here we review recent insights into the biophysical mechanisms involved in the reciprocal interplay between cells and the extracellular matrix and how this interplay determines tissue mechanics, with a focus on connective tissues. We first describe the roles of the main macromolecular components of the extracellular matrix in regards to tissue mechanics. We then proceed to highlight the main routes via which cells sense and respond to their biochemical and mechanical extracellular environment. Next we introduce the three main routes via which cells can modify their extracellular environment: exertion of contractile forces, secretion and deposition of matrix components, and matrix degradation. Finally we discuss how recent insights in the mechanobiology of cell-matrix interactions are furthering our understanding of the pathophysiology of connective tissue diseases and cancer, and facilitating the design of novel strategies for tissue engineering.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2022-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39834599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Let it rip: the mechanics of self-bisection in asexual planarians determines their population reproductive strategies.","authors":"Tapan Goel,&nbsp;Danielle Ireland,&nbsp;Vir Shetty,&nbsp;Christina Rabeler,&nbsp;Patrick H Diamond,&nbsp;Eva-Maria S Collins","doi":"10.1088/1478-3975/ac2f29","DOIUrl":"https://doi.org/10.1088/1478-3975/ac2f29","url":null,"abstract":"<p><p>Asexual freshwater planarians reproduce by transverse bisection (binary fission) into two pieces. This process produces a head and a tail, which fully regenerate within 1-2 weeks. How planarians split into two offspring-using only their musculature and substrate traction-is a challenging biomechanics problem. We found that three different species,<i>Dugesia japonica</i>,<i>Girardia tigrina</i>and<i>Schmidtea mediterranea</i>, have evolved three different mechanical solutions to self-bisect. Using time lapse imaging of the fission process, we quantitatively characterize the main steps of division in the three species and extract the distinct and shared key features. Across the three species, planarians actively alter their body shape, regulate substrate traction, and use their muscles to generate tensile stresses large enough to overcome the ultimate tensile strength of the tissue. Moreover, we show that<i>how</i>each planarian species divides dictates how resources are split among its offspring. This ultimately determines offspring survival and reproductive success. Thus, heterospecific differences in the mechanics of self-bisection of individual worms explain the observed differences in the population reproductive strategies of different planarian species.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"19 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2021-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39509815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphogen-regulated contact-mediated signaling between cells can drive the transitions underlying body segmentation in vertebrates.","authors":"Chandrashekar Kuyyamudi,&nbsp;Shakti N Menon,&nbsp;Sitabhra Sinha","doi":"10.1088/1478-3975/ac31a3","DOIUrl":"https://doi.org/10.1088/1478-3975/ac31a3","url":null,"abstract":"<p><p>We propose a unified mechanism that reproduces the sequence of dynamical transitions observed during somitogenesis, the process of body segmentation during embryonic development, that is invariant across all vertebrate species. This is achieved by combining inter-cellular interactions mediated via receptor-ligand coupling with global spatial heterogeneity introduced through a morphogen gradient known to occur along the anteroposterior axis. Our model reproduces synchronized oscillations in the gene expression in cells at the anterior of the presomitic mesoderm as it grows by adding new cells at its posterior, followed by travelling waves and subsequent arrest of activity, with the eventual appearance of somite-like patterns. This framework integrates a boundary-organized pattern formation mechanism, which uses positional information provided by a morphogen gradient, with the coupling-mediated self-organized emergence of collective dynamics, to explain the processes that lead to segmentation.</p>","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":"19 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2021-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39534392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}