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Stretching an elastic material along one axis typically induces contraction along the transverse axes, a phenomenon known as the Poisson effect. From these strains, one can compute the specific volume, which generally either increases or, in the incompressible limit, remains constant as the material is stretched. However, in networks of semiflexible or stiff polymers, which are typically highly compressible yet stiffen significantly when stretched, one instead sees a significant reduction in specific volume under finite strains. This volume reduction is accompanied by increasing alignment of filaments along the strain axis and a nonlinear elastic response, with stiffening of the apparent Young's modulus. For semiflexible networks, in which entropic bending elasticity governs the linear elastic regime, the nonlinear Poisson effect is caused by the nonlinear force-extension relationship of the constituent filaments, which produces a highly asymmetric response of the constituent polymers to stretching and compression. The details of this relationship depend on the geometric and elastic properties of the underlying filaments, which can vary greatly in experimental systems. Here, we provide a comprehensive characterization of the nonlinear Poisson effect in an affine network model and explore the influence of filament properties on essential features of both microscopic and macroscopic response, including strain-driven alignment and volume reduction.

Fibrous networks such as collagen are common in biological systems. Recent theoretical and experimental efforts have shed light on the mechanics of single component networks. Most real biopolymer networks, however, are composites made of elements with different rigidity. For instance, the extracellular matrix in mammalian tissues consists of stiff collagen fibers in a background matrix of flexible polymers such as hyaluronic acid (HA). The interplay between different biopolymer components in such composite networks remains unclear. In this work, we use 2D coarse-grained models to study the nonlinear strain-stiffening behavior of composites. We introduce a local volume constraint to model the incompressibility of HA. We also perform rheology experiments on composites of collagen with HA. Theoretically and experimentally, we demonstrate that the linear shear modulus of composite networks can be increased by approximately an order of magnitude above the corresponding moduli of the pure components. Our model shows that this synergistic effect can be understood in terms of the local incompressibility of HA, which acts to suppress density fluctuations of the collagen matrix with which it is entangled., (© 2024. The Author(s), under exclusive licence to EDP Sciences, SIF and Springer-Verlag GmbH Germany, part of Springer Nature.)

In active materials, uncoordinated internal stresses lead to emergent long-range flows. An understanding of how the behavior of active materials depends on mesoscopic (hydrodynamic) parameters is developing, but there remains a gap in knowledge concerning how hydrodynamic parameters depend on the properties of microscopic elements. In this work, we combine experiments and multiscale modeling to relate the structure and dynamics of active nematics composed of biopolymer filaments and molecular motors to their microscopic properties, in particular motor processivity, speed, and valency. We show that crosslinking of filaments by both motors and passive crosslinkers not only augments the contributions to nematic elasticity from excluded volume effects but dominates them. By altering motor kinetics we show that a competition between motor speed and crosslinking results in a nonmonotonic dependence of nematic flow on motor speed. By modulating passive filament crosslinking we show that energy transfer into nematic flow is in large part dictated by crosslinking. Thus motor proteins both generate activity and contribute to nematic elasticity. Our results provide new insights for rationally engineering active materials.

Networks and dense suspensions frequently reside near a boundary between soft (or fluidlike) and rigid (or solidlike) regimes. Transitions between these regimes can be driven by changes in structure, density, or applied stress or strain. In general, near the onset or loss of rigidity in these systems, dissipation-limiting heterogeneous nonaffine rearrangements dominate the macroscopic viscoelastic response, giving rise to diverging relaxation times and power-law rheology. Here, we describe a simple quantitative relationship between nonaffinity and the excess viscosity. We test this nonaffinity-viscosity relationship computationally and demonstrate its rheological consequences in simulations of strained filament networks and dense suspensions. We also predict critical signatures in the rheology of semiflexible and stiff biopolymer networks near the strain stiffening transition.

In active materials, uncoordinated internal stresses lead to emergent long-range flows. An understanding of how the behavior of active materials depends on mesoscopic (hydrodynamic) parameters is developing, but there remains a gap in knowledge concerning how hydrodynamic parameters depend on the properties of microscopic elements. In this work, we combine experiments and multiscale modeling to relate the structure and dynamics of active nematics composed of biopolymer filaments and molecular motors to their microscopic properties, in particular motor processivity, speed, and valency. We show that crosslinking of filaments by both motors and passive crosslinkers not only augments the contributions to nematic elasticity from excluded volume effects but dominates them. By altering motor kinetics we show that a competition between motor speed and crosslinking results in a nonmonotonic dependence of nematic flow on motor speed. By modulating passive filament crosslinking we show that energy transfer into nematic flow is in large part dictated by crosslinking. Thus motor proteins both generate activity and contribute to nematic elasticity. Our results provide new insights for rationally engineering active materials.

Disordered networks of semiflexible filaments are common support structures in biology. Familiar examples include fibrous matrices in blood clots, bacterial biofilms, and essential components of cells and tissues of plants, animals, and fungi. Despite the ubiquity of these networks in biomaterials, we have only a limited understanding of the relationship between their structural features and their highly strain-sensitive mechanical properties. In this work, we perform simulations of three-dimensional networks produced by the irreversible formation of cross-links between linker-decorated semiflexible filaments. We characterize the structure of networks formed by a simple diffusion-dependent assembly process and measure their associated steady-state rheological features at finite temperature over a range of applied prestrains that encompass the strain-stiffening transition. We quantify the dependence of network connectivity on cross-linker availability and detail the associated connectivity dependence of both linear elasticity and nonlinear strain-stiffening behavior, drawing comparisons with prior experimental measurements of the cross-linker concentration-dependent elasticity of actin gels.

Flocking in d=2 is a genuine nonequilibrium phenomenon for which irreversibility is an essential ingredient. We study a class of minimal flocking models whose only source of irreversibility is self-propulsion and use the entropy production rate (EPR) to quantify the departure from equilibrium across their phase diagrams. The EPR is maximal in the vicinity of the order-disorder transition, where reshuffling of the interaction network is fast. We show that signatures of irreversibility come in the form of asymmetries in the steady-state distribution of the flock's microstates. These asymmetries occur as consequences of the time-reversal symmetry breaking in the considered self-propelled systems, independently of the interaction details. In the case of metric pairwise forces, they reduce to local asymmetries in the distribution of pairs of particles. This study suggests a possible use of pair asymmetries both to quantify the departure from equilibrium and to learn relevant information about aligning interaction potentials from data.

In this work, we investigate whether stiffening in compression is a feature of single cells and whether the intracellular polymer networks that comprise the cytoskeleton (all of which stiffen with increasing shear strain) stiffen or soften when subjected to compressive strains. We find that individual cells, such as fibroblasts, stiffen at physiologically relevant compressive strains, but genetic ablation of vimentin diminishes this effect. Further, we show that unlike networks of purified F-actin or microtubules, which soften in compression, vimentin intermediate filament networks stiffen in both compression and extension, and we present a theoretical model to explain this response based on the flexibility of vimentin filaments and their surface charge, which resists volume changes of the network under compression. These results provide a new framework by which to understand the mechanical responses of cells and point to a central role of intermediate filaments in response to compression.

When subject to applied strain, fiber networks exhibit nonlinear elastic stiffening. Recent theory and experiments have shown that this phenomenon is controlled by an underlying mechanical phase transition that is critical in nature. Growing simulation evidence points to non-mean-field behavior for this transition and a hyperscaling relation has been proposed to relate the corresponding critical exponents. Here, we report simulations on two distinct network structures in three dimensions. By performing a finite-size scaling analysis, we test hyperscaling and identify various critical exponents. From the apparent validity of hyperscaling, as well as the non-mean-field exponents we observe, our results suggest that the upper critical dimension for the strain-controlled phase transition is above three, in contrast to the jamming transition that represents another athermal, mechanical phase transition.

Tissues commonly consist of cells embedded within a fibrous biopolymer network. Whereas cell-free reconstituted biopolymer networks typically soften under applied uniaxial compression, various tissues, including liver, brain, and fat, have been observed to instead stiffen when compressed. The mechanism for this compression-stiffening effect is not yet clear. Here, we demonstrate that when a material composed of stiff inclusions embedded in a fibrous network is compressed, heterogeneous rearrangement of the inclusions can induce tension within the interstitial network, leading to a macroscopic crossover from an initial bending-dominated softening regime to a stretching-dominated stiffening regime, which occurs before and independently of jamming of the inclusions. Using a coarse-grained particle-network model, we first establish a phase diagram for compression-driven, stretching-dominated stress propagation and jamming in uniaxially compressed two- and three-dimensional systems. Then, we demonstrate that a more detailed computational model of stiff inclusions in a subisostatic semiflexible fiber network exhibits quantitative agreement with the predictions of our coarse-grained model as well as qualitative agreement with experiments., Competing Interests: The authors declare no competing interest.

Fibrous networks such as collagen are common in physiological systems. One important function of these networks is to provide mechanical stability for cells and tissues. At physiological levels of connectivity, such networks would be mechanically unstable with only central-force interactions. While networks can be stabilized by bending interactions, it has also been shown that they exhibit a critical transition from floppy to rigid as a function of applied strain. Beyond a certain strain threshold, it is predicted that underconstrained networks with only central-force interactions exhibit a discontinuity in the shear modulus. We study the finite-size scaling behavior of this transition and identify both the mechanical discontinuity and critical exponents in the thermodynamic limit. We find both non-mean-field behavior and evidence for a hyperscaling relation for the critical exponents, for which the network stiffness is analogous to the heat capacity for thermal phase transitions. Further evidence for this is also found in the self-averaging properties of fiber networks.

Under extensional strain, fiber networks can exhibit an anomalously large and nonlinear Poisson effect accompanied by a dramatic transverse contraction and volume reduction for applied strains as small as a few percent. We demonstrate that this phenomenon is controlled by a collective mechanical phase transition that occurs at a critical uniaxial strain that depends on network connectivity. This transition is punctuated by an anomalous peak in the apparent Poisson's ratio and other critical signatures such as diverging nonaffine strain fluctuations.

As a function of connectivity, spring networks exhibit a critical transition between floppy and rigid phases at an isostatic threshold. For connectivity below this threshold, fiber networks were recently shown theoretically to exhibit a rigidity transition with corresponding critical signatures as a function of strain. Experimental collagen networks were also shown to be consistent with these predictions. We develop a scaling theory for this strain-controlled transition. Using a real-space renormalization approach, we determine relations between the critical exponents governing the transition, which we verify for the strain-controlled transition using numerical simulations of both triangular lattice-based and packing-derived fiber networks.

The mechanics of disordered fibrous networks such as those that make up the extracellular matrix are strongly dependent on the local connectivity or coordination number. For biopolymer networks this coordination number is typically between 3 and 4. Such networks are sub-isostatic and linearly unstable to deformation with only central force interactions, but exhibit a mechanical phase transition between floppy and rigid states under strain. The introduction of weak bending interactions stabilizes these networks and suppresses the critical signatures of this transition. We show that applying external stress can also stabilize subisostatic networks with only tensile central force interactions, i.e., a ropelike potential. Moreover, we find that the linear shear modulus shows a power-law scaling with the external normal stress, with a non-mean-field exponent. For networks with finite bending rigidity, we find that the critical stain shifts to lower values under prestress.

Hydrogels of semiflexible biopolymers such as collagen have been shown to contract axially under shear strain, in contrast to the axial dilation observed for most elastic materials. Recent work has shown that this behavior can be understood in terms of the porous, two-component nature and consequent time-dependent compressibility of hydrogels. The apparent normal stress measured by a torsional rheometer reflects only the tensile contribution of the axial component σzz on long (compressible) timescales, crossing over to the first normal stress difference, N1 = σxx - σzz at short (incompressible) times. While the behavior of N1 is well understood for isotropic viscoelastic materials undergoing affine shear deformation, biopolymer networks are often anisotropic and deform nonaffinely. Here, we numerically study the normal stresses that arise under shear in subisostatic, athermal semiflexible polymer networks. We show that such systems exhibit strong deviations from affine behavior and that these anomalies are controlled by a rigidity transition as a function of strain.

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus., (© The Author(s) 2015.)

Detection and elimination of calves and cows persistently infected with bovine viral diarrhea virus (BVDV) is important for the control of this pathogen. Historically, BVDV detection involved cell culture isolation followed by virus detection through immunofluorescence or immunoperoxidase monolayer assay (IPMA) methods. More recently, immunohistochemistry (IHC) has been added as a routine test for BVDV detection. The detection of BVDV by gel-based reverse transcription polymerase chain reaction (RT-PCR) is more sensitive and rapid than by cell culture isolation, but test results can be compromised by sample contamination during nucleic acid amplification. This study was designed to develop a closed-tube format of BVDV nucleic acid amplification and detection, TaqMan RT-PCR. The results of this new technique were compared with those obtained with virus isolation, IPMA, and IHC. With TaqMan RT-PCR, BVDV was detected in many samples negative by IPMA, IHC, and virus isolation with the exception of 1 sample that was positive by IHC. TaqMan RT-PCR in a closed-tube format offers a rapid, economical, high volume, and sensitive method for BVDV detection without the concerns of amplified cDNA product contamination associated with open-tube gel-based PCR tests.

Neonatal pigs from three herds of pigs were somnolent and inappetent and had microscopic lesions characterised by severe meningoencephalitis, necrotic interstitial pneumonia and gastric muscular inflammation. Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed and confirmed by virus isolation, fluorescent antibody examination of frozen lung sections, serology, immunohistochemistry and in situ hybridisation. Each herd had a history of PRRSV infection and was using or had used a modified-live vaccine. The isolates from the affected pigs were genetically distinct from the modified-live vaccine strain of the virus when compared by restriction enzyme analysis and nucleotide sequencing of PRRSV open reading frames 5 and 6. The virus was identified in macrophages or microglia of brain lesions by immunohistochemical staining of brain sections with an anti-PRRSV monoclonal antibody and an anti-macrophage antibody. The replication of the virus in the brain was verified by in situ hybridisation. The meningoencephalitis induced by the virus in pigs from each of the herds was unusually severe and the brain lesions were atypical when compared with other descriptions of encephalitis induced by the virus, which should therefore be considered as a possible diagnosis for neonatal pigs with severe meningoencephalitis. In addition, field isolates of the virus which are capable of causing disease can emerge and coexist with modified-live vaccine virus in some pig herds.

Previous studies have indicated that porcine reproductive and respiratory syndrome virus (PRRSV) can be identified in and transmitted through boar semen. However, the site(s) of replication indicating the origin of PRRSV in semen has not been identified. To determine how PRRSV enters boar semen, five vasectomized and two nonvasectomized PRRSV-seronegative boars were intranasally inoculated with PRRSV isolate VR-2332. Semen was collected three times weekly from each boar and separated into cellular and cell-free (seminal plasma) fractions. Both fractions were evaluated by reverse transcriptase nested polymerase chain reaction (RT-nPCR) for the presence of PRRSV RNA. Viremia and serostatus were evaluated once weekly, and boars were euthanatized 21 days postinoculation (DPI). Tissues were collected and evaluated by RT-nPCR, virus isolation (VI), and immunohistochemistry to identify PRRSV RNA, infectious virus, or viral antigen, respectively. PRRSV RNA was identified in semen from all vasectomized and nonvasectomized boars and was most consistently found in the cell fraction, within cells identified with a macrophage marker. Viral replication as determined by VI was predominately found within lymphoid tissue. However, PRRSV RNA was widely disseminated throughout many tissues, including the reproductive tract at 21 DPI. These results indicate that PRRSV can enter semen independent of testicular or epididymal tissues, and the source of PRRSV in semen is virus-infected monocytes/macrophages or non-cell-associated virus in serum. PRRSV-infected macrophages in semen may result from infection of local tissue macrophages or may originate from PRRSV-infected circulating monocytes or macrophages.

We characterized the lymphocytes in the tarsal joint synovium of chickens inoculated with an arthrotropic strain of avian reovirus. Cryostat sections of whole joints taken from 2 days to 35 days postinoculation were analyzed using monoclonal antibodies directed against B lymphocytes, T lymphocytes, and chicken Ia antigen. Plasma cells were morphologically identified using stained sections of whole joints. Time-dependent changes were found in the type and number of positively staining cells. Synoviocytes and cells with a dendritic morphology stained positive for Ia in normal joint sections. T cells, mostly CD8 positive, were present in low numbers in acute phase arthritis (2-6 days postinfection) in the perivascular and superficial regions of the synovium. Subacute arthritis (8-14 days postinfection) was characterized by increased numbers of CD4 and Cd8 T cells in the perivascular and superficial regions. The perivascular T cells began to organize into aggregates, with IgM-positive B cells and plasma cells on the periphery of these aggregates. Some CD8-positive cells were detected on the surface of the articular cartilage. Cells staining positively for Ia were not lymphocytes. Chronic arthritis ( > 14 days postinfection) was characterized by large numbers of T cells in the perivascular and superficial regions, with the CD4-positive T cells found primarily in the lymphoid aggregates of the perivascular regions. IgM-positive B cells were fewer, but more plasma cells, few of which stained positive for IgM, were present. Lymphocytes in chronic arthritis stained positively for Ia. These data suggest that the types, numbers, and activation level of lymphocytes present in the tarsal joints are similar but not identical to those seen in rheumatoid arthritis.

Serum and seminal plasma concentrations or activities of acid phosphatase (AP), prostate specific antigen (PSA), and canine prostate specific esterase (CPSE) were measured in normal dogs, dogs with benign prostatic hyperplasia (BPH), dogs with bacterial prostatitis, and dogs with prostatic carcinoma to determine if these assays would be of value in differentiating dogs with prostatic carcinoma from normal dogs, and dogs with other prostatic disorders. In addition, tissue sections of prostatic adenocarcinomas were stained with antiprostatic AP, anti-CPSE, and anti-PSA antibodies to determine if these would be suitable immunohistochemical markers of prostatic carcinoma. Prostate-specific antigen was not detected in canine serum or seminal plasma. Serum and seminal AP activities did not differ significantly between normal dogs and those with prostatic diseases, or among dogs with different prostatic disorders. Serum CPSE activities were significantly higher in dogs with BPH than in normal dogs. Mean serum CPSE activities in dogs with BPH, bacterial prostatitis, and prostatic carcinoma were not significantly different from each other. Slight to moderate immunohistochemical staining of canine prostatic adenocarcinomas was noted for prostatic AP and PSA; most tumors did not stain for CPSE. These results show that proteins of prostatic origin appear in the serum of dogs as a result of prostatic pathology, especially BPH. Canine prostatic adenocarcinoma does not appear to be associated with significant increases in CPSE or AP activities, possibly because of down-regulation of these enzymes by prostatic carcinoma cells. It is also possible that failure to detect significant differences resulted from limited statistical power for some groups and pairwise analyses because of the small number of dogs evaluated.

Tibial dyschondroplasia was induced in broiler chickens by oral administration of fusarochromanone, the toxic component of Fusarium equiseti. In two experiments, the activity of acid phosphatase in chondroclasts was assessed histochemically. Chicks were examined at 7, 14, 21, and 28 days of treatment in Expt. 1 and at 2, 4, and 6 days of treatment in Expt. 2. The staining for acid phosphatase was consistently lower in fusarochromanone-treated chicks after 2 days of treatment than in age-matched controls, and the onset of this difference corresponded to the onset of lesions. However, the decrease in acid phosphatase staining intensity was significant only at day 21 in Expt. 1 and at day 6 in Expt. 2. The deficiency of acid phosphatase in chondroclasts was judged to be of insufficient magnitude to account for the accumulation of growth plate cartilage that characterizes tibial dyschondroplasia.