103 research outputs found
Mechanics of bundled semiflexible polymer networks
While actin bundles are used by living cells for structural fortification,
the microscopic origin of the elasticity of bundled networks is not understood.
Here, we show that above a critical concentration of the actin binding protein
fascin, a solution of actin filaments organizes into a pure network of bundles.
While the elasticity of weakly crosslinked networks is dominated by the affine
deformation of tubes, the network of bundles can be fully understood in terms
of non-affine bending undulations.Comment: 5 pages, 3 figures, final version as publishe
Force-extension relation of cross-linked anisotropic polymer networks
Cross-linked polymer networks with orientational order constitute a wide
class of soft materials and are relevant to biological systems (e.g., F-actin
bundles). We analytically study the nonlinear force-extension relation of an
array of parallel-aligned, strongly stretched semiflexible polymers with random
cross-links. In the strong stretching limit, the effect of the cross-links is
purely entropic, independent of the bending rigidity of the chains. Cross-links
enhance the differential stretching stiffness of the bundle. For hard
cross-links, the cross-link contribution to the force-extension relation scales
inversely proportional to the force. Its dependence on the cross-link density,
close to the gelation transition, is the same as that of the shear modulus. The
qualitative behavior is captured by a toy model of two chains with a single
cross-link in the middle.Comment: 7 pages, 4 figure
Size-dependent rheology of type-I collagen networks
We investigate the system size dependent rheological response of branched
type I collagen gels. When subjected to a shear strain, the highly
interconnected mesh dynamically reorients, resulting in overall stiffening of
the network. When a continuous shear strain is applied to a collagen network,
we observe that the local apparent modulus, in the strain-stiffening regime, is
strongly dependent on the gel thickness. In addition, we demonstrate that the
overall network failure is determined by the ratio of the gel thickness to the
mesh size. These findings have broad implications for cell-matrix interactions,
the interpretation of rheological tissue data, and the engineering of
biomimetic scaffolds.Comment: 3 pages, 4 figures, to appear in Biophysical Journal Letters,
September 201
Single-crosslink microscopy in a biopolymer network dissects local elasticity from molecular fluctuations
Polymer networks are fundamental from cellular biology to plastics technology but their intrinsic inhomogeneity is masked by the usual ensemble-averaged measurements. Here, we construct direct maps of crosslinks-symbolic depiction of spatially-distributed elements highlighting their physical features and the relationships between them-in an actin network. We selectively label crosslinks with fluorescent markers, track their thermal fluctuations, and characterize the local elasticity and cross-correlations between crosslinks. Such maps display massive heterogeneity, reveal abundant anticorrelations, and may contribute to address how local responses scale up to produce macroscopic elasticity. Single-crosslink microscopy offers a general, microscopic framework to better understand crosslinked molecular networks in undeformed or strained states
Cervical Mucus Properties Stratify Risk for Preterm Birth
Background:
Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth.
Methods and Findings:
To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus.
Conclusions:
Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.Massachusetts Institute of Technology. Charles E. Reed Faculty Initiative FundBurroughs Wellcome Fund (Preterm Birth Research Grant)National Science Foundation (U.S.). Graduate Research Fellowship Progra
Mucin Biopolymers As Broad-Spectrum Antiviral Agents
Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system.National Institutes of Health (U.S.) (grant P30-ES002109)National Institutes of Health (U.S.) (grant P50-GM068763)German Academic Exchange Service (Postdoctoral fellowship
Carbohydrate hydrogels with stabilized phage particles for bacterial biosensing: bacterium diffusion studies
Bacteriophage particles have been reported as potentially useful in the development of diagnosis tools for pathogenic bacteria as they specifically recognize and lyse bacterial isolates thus confirming the presence of viable cells. One of the most representative microorganisms associated with health care services is the bacterium Pseudomonas aeruginosa, which alone is responsible for nearly 15 % of all nosocomial infections. In this context, structural and functional stabilization of phage particles within biopolymeric hydrogels, aiming at producing cheap (chromogenic) bacterial biosensing devices, has been the goal of a previous research effort. For this, a detailed knowledge of the bacterial diffusion profile into the hydrogel core, where the phage particles lie, is of utmost importance. In the present research effort, the bacterial diffusion process into the biopolymeric hydrogel core was mathematically described and the theoretical simulations duly compared with experimental results, allowing determination of the effective diffusion coefficients of P. aeruginosa in the agar and calcium alginate hydrogels tested.Financial support to Victor M. Balcao, via an Invited Research Scientist fellowship (FAPESP Ref. No. 2011/51077-8) by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Sao Paulo, Brazil), is hereby gratefully acknowledged
Elastically driven, intermittent microscopic dynamics in soft solids
Soft solids with tunable mechanical response are at the core of new material
technologies, but a crucial limit for applications is their progressive aging
over time, which dramatically affects their functionalities. The generally
accepted paradigm is that such aging is gradual and its origin is in slower
than exponential microscopic dynamics, akin to the ones in supercooled liquids
or glasses. Nevertheless, time- and space-resolved measurements have provided
contrasting evidence: dynamics faster than exponential, intermittency, and
abrupt structural changes. Here we use 3D computer simulations of a microscopic
model to reveal that the timescales governing stress relaxation respectively
through thermal fluctuations and elastic recovery are key for the aging
dynamics. When thermal fluctuations are too weak, stress heterogeneities
frozen-in upon solidification can still partially relax through elastically
driven fluctuations. Such fluctuations are intermittent, because of strong
correlations that persist over the timescale of experiments or simulations,
leading to faster than exponential dynamics.Comment: 7 pages, Supplementary Information include
Insight into the Assembly Properties and Functional Organisation of the Magnetotactic Bacterial Actin-like Homolog, MamK
Magnetotactic bacteria (MTB) synthesize magnetosomes, which are intracellular vesicles comprising a magnetic particle. A series of magnetosomes arrange themselves in chains to form a magnetic dipole that enables the cell to orient itself along the Earth’s magnetic field. MamK, an actin-like homolog of MreB has been identified as a central component in this organisation. Gene deletion, fluorescence microscopy and in vitro studies have yielded mechanistic differences in the filament assembly of MamK with other bacterial cytoskeletal proteins within the cell. With little or no information on the structural and behavioural characteristics of MamK outside the cell, the mamK gene from Magnetospirillium gryphiswaldense was cloned and expressed to better understand the differences in the cytoskeletal properties with its bacterial homologues MreB and acitin. Despite the low sequence identity shared between MamK and MreB (22%) and actin (18%), the behaviour of MamK monitored by light scattering broadly mirrored that of its bacterial cousin MreB primarily in terms of its pH, salt, divalent metal-ion and temperature dependency. The broad size variability of MamK filaments revealed by light scattering studies was supported by transmission electron microscopy (TEM) imaging. Filament morphology however, indicated that MamK conformed to linearly orientated filaments that appeared to be distinctly dissimilar compared to MreB suggesting functional differences between these homologues. The presence of a nucleotide binding domain common to actin-like proteins was demonstrated by its ability to function both as an ATPase and GTPase. Circular dichroism and structural homology modelling showed that MamK adopts a protein fold that is consistent with the ‘classical’ actin family architecture but with notable structural differences within the smaller domains, the active site region and the overall surface electrostatic potential
Diversity of actin architecture in human osteoclasts: network of curved and branched actin supporting cell shape and intercellular micrometer-level tubes
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