Mechanics of collective unfolding

Mechanically induced unfolding of passive crosslinkers is a fundamental biological phenomenon encountered across the scales from individual macro-molecules to cytoskeletal actin networks. In this paper we study a conceptual model of athermal load-induced unfolding and use a minimalistic setting allowing one to emphasize the role of long-range interactions while maintaining full analytical transparency. Our model can be viewed as a description of a parallel bundle of N bistable units confined between two shared rigid backbones that are loaded through a series spring. We show that the ground states in this model correspond to synchronized, single phase configurations where all individual units are either folded or unfolded. We then study the fine structure of the wiggly energy landscape along the reaction coordinate linking the two coherent states and describing the optimal mechanism of cooperative unfolding. Quite remarkably, our study shows the fundamental difference in the size and structure of the folding-unfolding energy barriers in the hard (fixed displacements) and soft (fixed forces) loading devices which persists in the continuum limit. We argue that both, the synchronization and the non-equivalence of the mechanical responses in hard and soft devices, have their origin in the dominance of long-range interactions. We then apply our minimal model to skeletal muscles where the power-stroke in acto-myosin crossbridges can be interpreted as passive folding. A quantitative analysis of the muscle model shows that the relative rigidity of myosin backbone provides the long-range interaction mechanism allowing the system to effectively synchronize the power-stroke in individual crossbridges even in the presence of thermal fluctuations. In view of the prototypical nature of the proposed model, our general conclusions pertain to a variety of other biological systems where elastic interactions are mediated by effective backbones

Thermodynamical framework for modeling chemo-mechanical coupling in muscle contraction – Formulation and preliminary results

International audienceWe propose a multiscale model of cardiac contraction in which the molecular motors at the origin of the contractile process are considered as multistable mechanical entities endowed with internal degrees of freedom of both mechanical and chemical nature. This model provides a thermodynamical basis for modeling the complex interplay of chemical and mechanical phenomena at the sub-cellular level. Important motivations for this work include the ability to represent the experimentally observed physiological characteristics of the contractile apparatus such as (i) the passive quick force recovery mechanism, (ii) the relation between the contraction velocity and the applied force and (iii) the so called Lymn-Taylor cycle describing the metabolism.Nous proposons un modèle multi-échelle de la contraction cardiaque dans lequel les moteurs moléculaires à l'origine du processus contractile sont représentés par des élé-ments mécaniques multistables paramétrés à la fois par des degrés de liberté géométriques et par des états chimiques. Ce modèle permet de poser les fondements thermody-namiques permettant de décrire l'interaction complexe entre les phénomènes mécaniques et chimiques a l'échelle sub-cellulaire. Ce travail a pour objet de représenter les car-actéristiques physiologiques du dispositif contractile observées expérimentalement et en particulier (i) le mécanisme passif de récupération rapide de force, (ii) la relation entre la vitesse de contraction et la charge appliquée et (iii) le cycle dit de Lymn-Taylor décrivant l'activité métabolique. Abstract : We propose a multiscale model of cardiac contraction in which the molecular motors at the origin of the contractile process are considered as multistable mechanical entities endowed with internal degrees of freedom of both mechanical and chemical nature. This model provides a thermodynamical basis for modeling the complex interplay of chemical and mechanical phenomena at the sub-cellular level. Important motivations for this work include the ability to represent the experimentally observed physiological characteristics of the contractile apparatus such as (i) the passive quick force recovery mechanism, (ii) the relation between the contraction velocity and the applied force and (iii) the so called Lymn-Taylor cycle describing the metabolism

Transport properties of water molecules confined between hydroxyapaptite surfaces: A Molecular dynamics simulation approach

Water diffusion in the vicinity of hydroxyapatite (HAP) crystals is a key issue to describe biomineralization process. In this study, a configuration of parallel HAP platelets mimicking bone nanopores is proposed to characterize the nanoscopic transport properties of water molecules at HAP-water surface and interfaces using various potential models such as combination of the Core-Shell (CS) model, Lennard-Jones (LJ) potentials with SPC or SPC/E water models. When comparing all these potentials models, it appears that the core-shell potential for HAP together with the SPC/E water model more accurately predicts the diffusion properties of water near HAP surface. Moreover, we have been able to put into relief the possibility of observing hydroxyl (OH−) ion dissociation that modifies the water structure near the HAP surfac

Joint data imputation and mechanistic modelling for simulating heart-brain interactions in incomplete datasets

The use of mechanistic models in clinical studies is limited by the lack of multi-modal patients data representing different anatomical and physiological processes. For example, neuroimaging datasets do not provide a sufficient representation of heart features for the modeling of cardiovascular factors in brain disorders. To tackle this problem we introduce a probabilistic framework for joint cardiac data imputation and personalisation of cardiovascular mechanistic models, with application to brain studies with incomplete heart data. Our approach is based on a variational framework for the joint inference of an imputation model of cardiac information from the available features, along with a Gaussian Process emulator that can faithfully reproduce personalised cardiovascular dynamics. Experimental results on UK Biobank show that our model allows accurate imputation of missing cardiac features in datasets containing minimal heart information, e.g. systolic and diastolic blood pressures only, while jointly estimating the emulated parameters of the lumped model. This allows a novel exploration of the heart-brain joint relationship through simulation of realistic cardiac dynamics corresponding to different conditions of brain anatomy

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few corrections to the published version, all in Appendix D.2 devoted to large deformation

Anisotropic diffusion of water molecules in hydroxyapatite nanopores

Funded by EPSRC Grant EP/K000128/1

Mécanique de la récupération rapide de force des muscles striés

This thesis is devoted to the modelling of transient response of muscle fibers submitted to fast mechanical loadings. At the nanometer scale, the muscle fiber contains actin and myosin filaments grouped to form contracile units called 'sarcomeres'. Myosin filament is an assembly of molecular motors that periodically attach and detach to the actin filament in presence of ATP. During this attachement-detachement process, myosin undergoes a force generating conformational change called the 'power-stroke' whose characteristics can be revealed by the transient responses following fast mechanical loadings. We propose an innovative mechanical model of a half sarcomere that links the characteristics of myosin to the response of the whole fiber. Unlike existing models, using a discrete approach, this model is based on the definition of a continuous energy landscape that takes into account a mean field interaction between the molecular motors. This system presents radically different responses under imposed length and imposed force conditions. We particularly emphasize a difference in the kinetics, also observed experimentally. We show that the half-sarcomere is inherently unstable which explains the sarcomere length inhomogeneities observed recently on myofibrils.Cette thèse est consacrée à la modélisation de la réponse transitoire d'une fibre musculaire squelettique soumise à des sollicitations mécaniques rapides. A l'échelle du nanomètre, la fibre musculaire contient des filaments d'actine et de myosine regroupés en unités contractiles appelées "sarcomères". Le filament de myosine est un assemblage de moteurs mol ́eculaires qui, en présence d'ATP, s'attachent et se d ́etachent p ́eriodiquement au filament d'actine. Au cours de ce processus d'attachement-détachement, la myosine génère une force lors d'un changement de conformation appelé "power-stroke". Ses caractéristiques peuvent être étudiées lors de la réponse transitoire de la fibre soumise à des sollicitations mécaniques rapides. Nous proposons un modèle mécanique innovant du demi-sarcomere permettant de relier les caractéristiques de la myosine à la réponse de la fibre complète. A la différence des modèles existants, privilégiant une approche discrète, ce modèle s'appuie sur la définition d'un potentiel d'énergie continu qui prend en compte une interaction de champ moyen entre les moteurs moléculaires. Ce système présente des réponses radicallement différentes à longueur imposée et à force imposée. Nous proposons en particulier une explication à la différence de cinétique observée expérimentalement. Nous montrons également que le demi-sarcomere est m ́ecaniquement instable ce qui explique les inhomogénéités de longueurs observées dans une myofibrille

Sur La Nouvelle Famille Des Scutellariacées

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Le Flora Italiana Et Ses Critiques

Volume: 36Start Page: 257End Page: 27

Classification Des Fruits

Volume: 33Start Page: 117End Page: 12