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1.
Methods Mol Biol ; 2187: 223-245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32770510

RESUMO

The study of the structure and dynamics of membrane domains in vivo is a challenging task. However, major advances could be achieved through the application of microscopic and spectroscopic techniques coupled with the use of model membranes, where the relations between lipid composition and the type, amount and properties of the domains present can be quantitatively studied.This chapter provides protocols to study membrane organization and visualize membrane domains by fluorescence microscopy both in artificial membrane and living cell models of Gaucher Disease (GD ). We describe a bottom-up multiprobe methodology, which enables understanding how the specific lipid interactions established by glucosylceramide, the lipid that accumulates in GD , affect the biophysical properties of model and cell membranes, focusing on its ability to influence the formation, properties and organization of lipid raft domains. In this context, we address the preparation of (1) raft-mimicking giant unilamellar vesicles labeled with a combination of fluorophores that allow for the visualization and comprehensive characterization of those membrane domains and (2) human fibroblasts exhibiting GD phenotype to assess the biophysical properties of biological membrane in living cells using fluorescence microscopy.


Assuntos
Biofísica/métodos , Bicamadas Lipídicas/metabolismo , Microdomínios da Membrana/metabolismo , Microscopia de Fluorescência/métodos , Membrana Celular/metabolismo , Células Cultivadas , Fibroblastos/metabolismo , Doença de Gaucher/metabolismo , Glucosilceramidas/metabolismo , Humanos , Pele/metabolismo , Lipossomas Unilamelares/metabolismo
2.
Methods Mol Biol ; 2187: 247-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32770511

RESUMO

The use of steady-state and time-resolved fluorescence spectroscopy to study sterol and sphingolipid-enriched lipid domains as diverse as the ones found in mammalian and fungal membranes is herein described. We first address how to prepare liposomes that mimic raft-containing membranes of mammalian cells and how to use fluorescence spectroscopy to characterize the biophysical properties of these membrane model systems. We further illustrate the application of Förster resonance energy transfer (FRET) to study nanodomain reorganization upon interaction with small bioactive molecules, phenolic acids, an important group of phytochemical compounds. This methodology overcomes the resolution limits of conventional fluorescence microscopy allowing for the identification and characterization of lipid domains at the nanoscale.We continue by showing how to use fluorescence spectroscopy in the biophysical analysis of more complex biological systems, namely the plasma membrane of Saccharomyces cerevisiae yeast cells and the necessary adaptations to the filamentous fungus Neurospora crassa , evaluating the global order of the membrane, sphingolipid-enriched domains rigidity and abundance, and ergosterol-dependent properties.


Assuntos
Biofísica/métodos , Membrana Celular/metabolismo , Mamíferos/metabolismo , Lipídeos de Membrana/metabolismo , Microdomínios da Membrana/metabolismo , Espectrometria de Fluorescência/métodos , Animais , Ergosterol/metabolismo , Transferência Ressonante de Energia de Fluorescência/métodos , Neurospora crassa/metabolismo , Saccharomyces cerevisiae/metabolismo , Esfingolipídeos/metabolismo , Esteróis/metabolismo
3.
Methods Mol Biol ; 2187: 283-301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32770513

RESUMO

Communication between cells and their environment is carried out through the plasma membrane including the action of most pharmaceutical drugs. Although such a communication typically involves specific binding of a messenger to a membrane receptor, the biophysical state of the lipid bilayer strongly influences the outcome of this interaction. Sphingolipids constitute an important part of the lipid membrane, and their mole fraction modifies the biophysical characteristics of the membrane. Here, we describe methods that can be used for measuring how sphingolipid accumulation alters the compactness, microviscosity, and dipole potential of the lipid bilayer and the mobility of membrane components.


Assuntos
Membrana Celular/metabolismo , Potenciais da Membrana/fisiologia , Esfingolipídeos/metabolismo , Biofísica/métodos , Linhagem Celular , Humanos , Bicamadas Lipídicas/metabolismo , Células THP-1/metabolismo , Viscosidade
5.
Nat Commun ; 11(1): 4108, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796840

RESUMO

Replicating biological patterns is promising for designing materials with multifaceted properties. Twisted cholesteric liquid crystal patterns are found in the iridescent tessellated cuticles of many insects and a few fruits. Their accurate replication is extremely difficult since discontinuous patterns and colors must coexist in a single layer without discontinuity of the structures. Here, a solution is demonstrated by addressing striped insect cuticles with a complex twisted organization. Geometric constraints are met by controlling the thermal diffusion in a cholesteric oligomer bilayer subjected to local changes in the molecular anchoring conditions. A multicriterion comparison reveals a very high level of biomimicry. Proof-of-concept prototypes of anti-counterfeiting tags are presented. The present design involves an economy of resources and a high versatility of chiral patterns unreached by the current manufacturing techniques such as metallic layer vacuum deposition, template embossing and various forms of lithography which are limited and often prohibitively expensive.


Assuntos
Biomimética/métodos , Biofísica/métodos , Cristais Líquidos/química , Óptica e Fotônica/métodos , Animais , Insetos
6.
PLoS Comput Biol ; 16(4): e1007709, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32343724

RESUMO

Mechanical interactions between flowing and coagulated blood (thrombus) are crucial in dictating the deformation and remodeling of a thrombus after its formation in hemostasis. We propose a fully-Eulerian, three-dimensional, phase-field model of thrombus that is calibrated with existing in vitro experimental data. This phase-field model considers spatial variations in permeability and material properties within a single unified mathematical framework derived from an energy perspective, thereby allowing us to study effects of thrombus microstructure and properties on its deformation and possible release of emboli under different hemodynamic conditions. Moreover, we combine this proposed thrombus model with a particle-based model which simulates the initiation of the thrombus. The volume fraction of a thrombus obtained from the particle simulation is mapped to an input variable in the proposed phase-field thrombus model. The present work is thus the first computational study to integrate the initiation of a thrombus through platelet aggregation with its subsequent viscoelastic responses to various shear flows. This framework can be informed by clinical data and potentially be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions.


Assuntos
Vasos Sanguíneos/fisiologia , Trombose/fisiopatologia , Biofísica/métodos , Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Simulação por Computador , Humanos , Modelos Biológicos , Adesividade Plaquetária/fisiologia , Agregação Plaquetária/fisiologia , Trombose/sangue
7.
Cell Physiol Biochem ; 54(3): 371-383, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32298554

RESUMO

BACKGROUND/AIMS: This study aimed to establish a precise and well-defined working model, assessing pharmaceutical effects on vascular smooth muscle cell monolayer in-vitro. It describes various analysis techniques to determine the most suitable to measure the biomechanical impact of vasoactive agents by using CellDrum technology. METHODS: The so-called CellDrum technology was applied to analyse the biomechanical properties of confluent human aorta muscle cells (haSMC) in monolayer. The cell generated tensions deviations in the range of a few N/m² are evaluated by the CellDrum technology. This study focuses on the dilative and contractive effects of L-type Ca2+ channel agonists and antagonists, respectively. We analyzed the effects of Bay K8644, nifedipine and verapamil. Three different measurement modes were developed and applied to determine the most appropriate analysis technique for the study purpose. These three operation modes are called, particular time mode" (PTM), "long term mode" (LTM) and "real-time mode" (RTM). RESULTS: It was possible to quantify the biomechanical response of haSMCs to the addition of vasoactive agents using CellDrum technology. Due to the supplementation of 100nM Bay K8644, the tension increased approximately 10.6% from initial tension maximum, whereas, the treatment with nifedipine and verapamil caused a significant decrease in cellular tension: 10nM nifedipine decreased the biomechanical stress around 6,5% and 50nM verapamil by 2,8%, compared to the initial tension maximum. Additionally, all tested measurement modes provide similar results while focusing on different analysis parameters. CONCLUSION: The CellDrum technology allows highly sensitive biomechanical stress measurements of cultured haSMC monolayers. The mechanical stress responses evoked by the application of vasoactive calcium channel modulators were quantified functionally (N/m²). All tested operation modes resulted in equal findings, whereas each mode features operation-related data analysis.


Assuntos
Biofísica/métodos , Músculo Liso Vascular/efeitos dos fármacos , Vasoconstritores/farmacologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Aorta/efeitos dos fármacos , Fenômenos Biomecânicos , Biofísica/instrumentação , Canais de Cálcio Tipo L/efeitos dos fármacos , Canais de Cálcio Tipo L/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Humanos , Nifedipino/farmacologia , Estresse Mecânico , Vasoconstrição , Verapamil/farmacologia
8.
Proc Natl Acad Sci U S A ; 117(18): 9699-9705, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32300006

RESUMO

A ubiquitous structural feature in biological systems is texture in extracellular matrix that gains functions when hardened, for example, cell walls, insect scales, and diatom tests. Here, we develop patterned liquid crystal elastomer (LCE) particles by recapitulating the biophysical patterning mechanism that forms pollen grain surfaces. In pollen grains, a phase separation of extracellular material into a pattern of condensed and fluid-like phases induces undulations in the underlying elastic cell membrane to form patterns on the cell surface. In this work, LCE particles with variable surface patterns were created through a phase separation of liquid crystal oligomers (LCOs) droplet coupled to homeotropic anchoring at the droplet interface, analogously to the pollen grain wall formation. Specifically, nematically ordered polydisperse LCOs and isotropic organic solvent (dichloromethane) phase-separate at the surface of oil-in-water droplets, while, different LCO chain lengths segregate to different surface curvatures simultaneously. This phase separation, which creates a distortion in the director field, is in competition with homeotropic anchoring induced by sodium dodecyl sulfate (SDS). By tuning the polymer chemistry of the system, we are able to influence this separation process and tune the types of surface patterns in these pollen-like microparticles. Our study reveals that the energetically favorable biological mechanism can be leveraged to offer simple yet versatile approaches to synthesize microparticles for mechanosensing, tissue engineering, drug delivery, energy storage, and displays.


Assuntos
Elastômeros/química , Cristais Líquidos/química , Microplásticos/química , Pólen/química , Biofísica/métodos , Matriz Extracelular/química , Cloreto de Metileno/química , Dodecilsulfato de Sódio/química , Propriedades de Superfície
9.
PLoS Comput Biol ; 16(4): e1007640, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32271761

RESUMO

This is a PLOS Computational Biology Education paper. The idea that the brain functions so as to minimize certain costs pervades theoretical neuroscience. Because a cost function by itself does not predict how the brain finds its minima, additional assumptions about the optimization method need to be made to predict the dynamics of physiological quantities. In this context, steepest descent (also called gradient descent) is often suggested as an algorithmic principle of optimization potentially implemented by the brain. In practice, researchers often consider the vector of partial derivatives as the gradient. However, the definition of the gradient and the notion of a steepest direction depend on the choice of a metric. Because the choice of the metric involves a large number of degrees of freedom, the predictive power of models that are based on gradient descent must be called into question, unless there are strong constraints on the choice of the metric. Here, we provide a didactic review of the mathematics of gradient descent, illustrate common pitfalls of using gradient descent as a principle of brain function with examples from the literature, and propose ways forward to constrain the metric.


Assuntos
Biofísica/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Biologia Computacional/métodos , Algoritmos , Simulação por Computador , Humanos , Processamento de Imagem Assistida por Computador , Cinética , Matemática , Redes Neurais de Computação , Neurociências/métodos
10.
Nat Commun ; 11(1): 1356, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170071

RESUMO

Nucleotide excision repair (NER) removes a wide range of DNA lesions, including UV-induced photoproducts and bulky base adducts. XPA is an essential protein in eukaryotic NER, although reports about its stoichiometry and role in damage recognition are controversial. Here, by PeakForce Tapping atomic force microscopy, we show that human XPA binds and bends DNA by ∼60° as a monomer. Furthermore, we observe XPA specificity for the helix-distorting base adduct N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene over non-damaged dsDNA. Moreover, single molecule fluorescence microscopy reveals that DNA-bound XPA exhibits multiple modes of linear diffusion between paused phases. The presence of DNA damage increases the frequency of pausing. Truncated XPA, lacking the intrinsically disordered N- and C-termini, loses specificity for DNA lesions and shows less pausing on damaged DNA. Our data are consistent with a working model in which monomeric XPA bends DNA, displays episodic phases of linear diffusion along DNA, and pauses in response to DNA damage.


Assuntos
DNA/química , DNA/metabolismo , Imagem Individual de Molécula/métodos , Proteína de Xeroderma Pigmentoso Grupo A/química , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo , Biofísica/métodos , Adutos de DNA/química , Adutos de DNA/metabolismo , Dano ao DNA/fisiologia , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/metabolismo , Humanos , Microscopia de Força Atômica , Ligação Proteica , Raios Ultravioleta
11.
Development ; 147(4)2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066591

RESUMO

The EMBO/EMBL Symposium 'Mechanical Forces in Development' was held in Heidelberg, Germany, on 3-6 July 2019. This interdisciplinary symposium brought together an impressive and diverse line-up of speakers seeking to address the origin and role of mechanical forces in development. Emphasising the importance of integrative approaches and theoretical simulations to obtain comprehensive mechanistic insights into complex morphogenetic processes, the meeting provided an ideal platform to discuss the concepts and methods of developmental mechanobiology in an era of fast technical and conceptual progress. Here, we summarise the concepts and findings discussed during the meeting, as well as the agenda it sets for the future of developmental mechanobiology.


Assuntos
Biofísica/métodos , Biofísica/tendências , Biologia do Desenvolvimento/métodos , Biologia do Desenvolvimento/tendências , Mecanotransdução Celular , Animais , Regulação da Expressão Gênica no Desenvolvimento , Alemanha , Homeostase , Humanos , Pesquisa Interdisciplinar , Modelos Biológicos , Morfogênese , Fenômenos Fisiológicos Vegetais , Estresse Mecânico
12.
Sci Rep ; 10(1): 1763, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019938

RESUMO

The running-specific prosthetic (RSP) configuration used by athletes with transtibial amputations (TTAs) likely affects performance. Athletes with unilateral TTAs are prescribed C- or J-shaped RSPs with a manufacturer-recommended stiffness category based on body mass and activity level, and height based on unaffected leg and residual limb length. We determined how 15 different RSP model, stiffness, and height configurations affect maximum running velocity (vmax) and the underlying biomechanics. Ten athletes with unilateral TTAs ran at 3 m/s to vmax on a force-measuring treadmill. vmax was 3.8-10.7% faster when athletes used J-shaped versus C-shaped RSP models (p < 0.05), but was not affected by stiffness category, actual stiffness (kN/m), or height (p = 0.72, p = 0.37, and p = 0.11, respectively). vmax differences were explained by vertical ground reaction forces (vGRFs), stride kinematics, leg stiffness, and symmetry. While controlling for velocity, use of J-shaped versus C-shaped RSPs resulted in greater stance average vGRFs, slower step frequencies, and longer step lengths (p < 0.05). Stance average vGRFs were less asymmetric using J-shaped versus C-shaped RSPs (p < 0.05). Contact time and leg stiffness were more asymmetric using the RSP model that elicited the fastest vmax (p < 0.05). Thus, RSP geometry (J-shape versus C-shape), but not stiffness or height, affects vmax in athletes with unilateral TTAs.


Assuntos
Amputação/reabilitação , Membros Artificiais , Perna (Membro)/fisiologia , Corrida/fisiologia , Adulto , Atletas , Fenômenos Biomecânicos , Biofísica/métodos , Teste de Esforço/métodos , Feminino , Nível de Saúde , Humanos , Masculino , Desenho de Prótese/métodos , Adulto Jovem
13.
Bioessays ; 42(2): e1900146, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31994772

RESUMO

Evolution exploits the physics of non-neural bioelectricity to implement anatomical homeostasis: a process in which embryonic patterning, remodeling, and regeneration achieve invariant anatomical outcomes despite external interventions. Linear "developmental pathways" are often inadequate explanations for dynamic large-scale pattern regulation, even when they accurately capture relationships between molecular components. Biophysical and computational aspects of collective cell activity toward a target morphology reveal interesting aspects of causation in biology. This is critical not only for unraveling evolutionary and developmental events, but also for the design of effective strategies for biomedical intervention. Bioelectrical controls of growth and form, including stochastic behavior in such circuits, highlight the need for the formulation of nuanced views of pathways, drivers of system-level outcomes, and modularity, borrowing from concepts in related disciplines such as cybernetics, control theory, computational neuroscience, and information theory. This approach has numerous practical implications for basic research and for applications in regenerative medicine and synthetic bioengineering.


Assuntos
Morfogênese/fisiologia , Regeneração/fisiologia , Animais , Bioengenharia/métodos , Biofísica/métodos , Homeostase/fisiologia , Humanos , Modelos Biológicos , Neurociências/métodos , Medicina Regenerativa/métodos
14.
J Mol Biol ; 432(2): 621-631, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31866291

RESUMO

Advances in molecular biology, optics, genetics, and bioinformatics have opened the door to mapping, in molecular detail, processes inside living cells. With the ability to observe the individual moving parts of cellular machinery, concepts formerly confined to physics are entering mainstream biology. This article discusses a few ideas of this sort related to chromosome biology, to illustrate what kinds of insights physics might yet bring to our understanding of living systems.


Assuntos
Cromossomos/genética , Biologia Molecular/métodos , Física/métodos , Biofísica/métodos , Cromossomos/ultraestrutura , Biologia Computacional/métodos , Humanos
15.
J Mol Biol ; 432(4): 845-860, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31874151

RESUMO

In light chain amyloidosis (AL), fibrillar deposition of monoclonal immunoglobulin light chains (LCs) in vital organs, such as heart, is associated with their severe dysfunction. In addition to the cellular damage caused by fibril deposition, direct toxicity of soluble prefibrillar amyloidogenic proteins has been reported, in particular, for cardiotoxicity. However, the molecular bases of proteotoxicity by soluble LCs have not been clarified. Here, to address this issue, we rationally engineered the amino acid sequence of the highly cardiotoxic LC H6 by introducing three residue mutations, designed to reduce the dynamics of its native state. The resulting mutant (mH6) is less toxic than its parent H6 to human cardiac fibroblasts and C. elegans. The high sequence and structural similarity, together with the different toxicity, make H6 and its non-toxic designed variant mH6 a test case to shed light on the molecular properties underlying soluble toxicity. Our comparative structural and biochemical study of H6 and mH6 shows closely matching crystal structures, whereas spectroscopic data and limited proteolysis indicate that H6 displays poorly cooperative fold, higher flexibility, and kinetic instability, and a higher dynamic state in its native fold. Taken together, the results of this study show a strong correlation between the overall conformational properties of the native fold and the proteotoxicity of cardiotropic LCs.


Assuntos
Amiloide/metabolismo , Amiloidose/metabolismo , Biofísica/métodos , Cadeias Leves de Imunoglobulina/química , Cadeias Leves de Imunoglobulina/metabolismo , Amiloide/química , Amiloide/genética , Amiloidose/genética , Animais , Humanos , Cadeias Leves de Imunoglobulina/genética , Mutação/genética , Dobramento de Proteína
16.
Int J Biostat ; 16(1)2019 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-31811802

RESUMO

We present new methods for cell line classification using multivariate time series bioimpedance data obtained from electric cell-substrate impedance sensing (ECIS) technology. The ECIS technology, which monitors the attachment and spreading of mammalian cells in real time through the collection of electrical impedance data, has historically been used to study one cell line at a time. However, we show that if applied to data from multiple cell lines, ECIS can be used to classify unknown or potentially mislabeled cells, factors which have previously been associated with the reproducibility crisis in the biological literature. We assess a range of approaches to this new problem, testing different classification methods and deriving a dictionary of 29 features to characterize ECIS data. Most notably, our analysis enriches the current field by making use of simultaneous multi-frequency ECIS data, where previous studies have focused on only one frequency; using classification methods to distinguish multiple cell lines, rather than simple statistical tests that compare only two cell lines; and assessing a range of features derived from ECIS data based on their classification performance. In classification tests on fifteen mammalian cell lines, we obtain very high out-of-sample predictive accuracy. These preliminary findings provide a baseline for future large-scale studies in this field.


Assuntos
Biofísica/métodos , Linhagem Celular/classificação , Técnicas Citológicas/métodos , Aprendizado de Máquina Supervisionado , Animais , Impedância Elétrica , Humanos
17.
Biol Cybern ; 113(5-6): 465-474, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31696303

RESUMO

Developing whole-brain emulation (WBE) technology would provide immense benefits across neuroscience, biomedicine, artificial intelligence, and robotics. At this time, constructing a simulated human brain lacks feasibility due to limited experimental data and limited computational resources. However, I suggest that progress toward this goal might be accelerated by working toward an intermediate objective, namely insect brain emulation (IBE). More specifically, this would entail creating biologically realistic simulations of entire insect nervous systems along with more approximate simulations of non-neuronal insect physiology to make "virtual insects." I argue that this could be realistically achievable within the next 20 years. I propose that developing emulations of insect brains will galvanize the global community of scientists, businesspeople, and policymakers toward pursuing the loftier goal of emulating the human brain. By demonstrating that WBE is possible via IBE, simulating mammalian brains and eventually the human brain may no longer be viewed as too radically ambitious to deserve substantial funding and resources. Furthermore, IBE will facilitate dramatic advances in cognitive neuroscience, artificial intelligence, and robotics through studies performed using virtual insects.


Assuntos
Encéfalo , Insetos , Modelos Neurológicos , Neurônios , Animais , Biofísica/métodos , Biofísica/tendências , Neurociências/métodos , Neurociências/tendências
18.
Life Sci ; 239: 117060, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31733317

RESUMO

Cancer has become a key healthcare problem worldwide. The background of cancer research has brought the advent of cross-disciplinary collaborations that has enabled us to get an idea of the disease mechanisms at spatial and temporal scales. Understanding the combination of biology and physics of cancer presents a promising field of research with apprehensions in better clarity over both cellular and molecular mechanisms impacting cancer therapy. Investigation of cancer biology has provided a wealth of knowledge on cancer initiation and propagation and has provided newer treatment strategies in the fight against cancer. Understanding the physics of cancer provides wonderful set of equations that take advantage of mechanisms of force production, propagation by the cancer cells and mechanical properties of the tumor tissue. The spatial tissue arrangement in which the tumor growth occurs can be better understood with biophysics. Thus, the combination of biology and physics of cancer contributes crucially in impacting the correct treatment of cancer. The present review is aimed at providing an overview of regulatory networks, regulation of cell division and differentiation, the signal transduction pathways and integration of all sciences including physics, biology, and medicine which is very well needed to tackle the war against cancer and thus influence cancer therapy. These circuits will help us understand whether the therapy will work wonders or cause failure. As cancer is much more than a genetic disease, more insights into the malignancy with physical approaches are designed to use cancer therapy effectively.


Assuntos
Biofísica/métodos , Neoplasias/metabolismo , Neoplasias/patologia , Biologia , Redes Reguladoras de Genes/genética , Humanos , Física , Transdução de Sinais/fisiologia
19.
Cell Rep ; 29(1): 1-12, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577940

RESUMO

Recent rapid progress in the field of mechanobiology has been driven by novel emerging tools and methodologies and growing interest from different scientific disciplines. Specific progress has been made toward understanding how cell mechanics is linked to intracellular signaling and the regulation of gene expression in response to a variety of mechanical stimuli. There is a direct link between the mechanoreceptors at the cell surface and intracellular biochemical signaling, which in turn controls downstream effector molecules. Among the mechanoreceptors in the cell membrane, mechanosensitive (MS) ion channels are essential for the ultra-rapid (millisecond) transduction of mechanical stimuli into biologically relevant signals. The three decades of research on mechanosensitive channels resulted in the formulation of two basic principles of mechanosensitive channel gating: force-from-lipids and force-from-filament. In this review, we revisit the biophysical principles that underlie the innate force-sensing ability of mechanosensitive channels as contributors to the force-dependent evolution of life forms.


Assuntos
Canais Iônicos/metabolismo , Mecanotransdução Celular/fisiologia , Animais , Biofísica/métodos , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Humanos , Mecanorreceptores/metabolismo , Transdução de Sinais/fisiologia
20.
Nat Commun ; 10(1): 4662, 2019 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604949

RESUMO

While ubiquitous, energy redistribution remains a poorly understood facet of the nonequilibrium thermodynamics of biomolecules. At the molecular level, finite-size effects, pronounced nonlinearities, and ballistic processes produce behavior that diverges from the macroscale. Here, we show that transient thermal transport reflects macromolecular energy landscape architecture through the topological characteristics of molecular contacts and the nonlinear processes that mediate dynamics. While the former determines transport pathways via pairwise interactions, the latter reflects frustration within the landscape for local conformational rearrangements. Unlike transport through small-molecule systems, such as alkanes, nonlinearity dominates over coherent processes at even quite short time- and length-scales. Our exhaustive all-atom simulations and novel local-in-time and space analysis, applicable to both theory and experiment, permit dissection of energy migration in biomolecules. The approach demonstrates that vibrational energy transport can probe otherwise inaccessible aspects of macromolecular dynamics and interactions that underly biological function.


Assuntos
Transferência de Energia , Simulação de Dinâmica Molecular , Biofísica/métodos , Biologia Computacional , Simulação por Computador , Cinética , Termodinâmica
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