Membrane Tension Regulation is Required for Wound Repair.

Disruptions of the eukaryotic plasma membrane due to chemical and mechanical challenges are frequent and detrimental and thus need to be repaired to maintain proper cell function and avoid cell death. However, the cellular mechanisms involved in wound resealing and restoration of homeostasis are diverse and contended. Here, it is shown that clathrin-mediated endocytosis is induced at later stages of plasma membrane wound repair following the actual resealing of the wound.

Characterizing intracellular mechanics via optical tweezers-based microrheology.

Intracellular organization is a highly regulated homeostatic state maintained to ensure eukaryotic cells' correct and efficient functioning. Thanks to decades of research, vast knowledge of the proteins involved in intracellular transport and organization has been acquired. However, how these influence and potentially regulate the intracellular mechanical properties of the cell is largely unknown.

Rapid and reversible optical switching of cell membrane area by an amphiphilic azobenzene.

Cellular membrane area is a key parameter for any living cell that is tightly regulated to avoid membrane damage. Changes in area-to-volume ratio are known to be critical for cell shape, but are mostly investigated by changing the cell volume via osmotic shocks. In turn, many important questions relating to cellular shape, membrane tension homeostasis and local membrane area cannot be easily addressed because experimental tools for controlled modulation of cell membrane area are lacking.

Primordial germ cells adjust their protrusion type while migrating in different tissue contexts in vivo.

In both physiological processes and disease contexts, migrating cells have the ability to adapt to conditions in their environment. As an in vivo model for this process, we use zebrafish primordial germ cells that migrate throughout the developing embryo. When migrating within an ectodermal environment, the germ cells form fewer and smaller blebs when compared with their behavior within mesodermal environment.

Nonswelling and Hydrolytically Stable Hydrogels Uncover Cellular Mechanosensing in 3D.

While matrix stiffness regulates cell behavior on 2D substrates, recent studies using synthetic hydrogels have suggested that in 3D environments, cell behavior is primarily impacted by matrix degradability, independent of stiffness. However, these studies did not consider the potential impact of other confounding matrix parameters that typically covary with changes in stiffness, particularly, hydrogel swelling and hydrolytic stability, which may explain the previously observed distinctions in cell response in 2D versus 3D settings. To investigate how cells sense matrix stiffness in 3D environments, a nonswelling, hydrolytically stable, linearly elastic synthetic hydrogel model is developed in which matrix stiffness and degradability can be tuned independently.

Pressure Drives Rapid Burst-Like Coordinated Cellular Motion from 3D Cancer Aggregates.

A key behavior observed during morphogenesis, wound healing, and cancer invasion is that of collective and coordinated cellular motion. Hence, understanding the different aspects of such coordinated migration is fundamental for describing and treating cancer and other pathological defects. In general, individual cells exert forces on their environment in order to move, and collective motion is coordinated by cell-cell adhesion-based forces.

Using migrating cells as probes to illuminate features in live embryonic tissues.

The biophysical and biochemical properties of live tissues are important in the context of development and disease. Methods for evaluating these properties typically involve destroying the tissue or require specialized technology and complicated analyses. Here, we present a novel, noninvasive methodology for determining the spatial distribution of tissue features within embryos, making use of nondirectionally migrating cells and software we termed "Landscape," which performs automatized high-throughput three-dimensional image registration.

E-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow.

The migration of many cell types relies on the formation of actomyosin-dependent protrusions called blebs, but the mechanisms responsible for focusing this kind of protrusive activity to the cell front are largely unknown. Here, we employ zebrafish primordial germ cells (PGCs) as a model to study the role of cell-cell adhesion in bleb-driven single-cell migration in vivo. Utilizing a range of genetic, reverse genetic and mathematical tools, we define a previously unknown role for E-cadherin in confining bleb-type protrusions to the leading edge of the cell.

Revealing the molecular origins of fibrin's elastomeric properties by in situ X-ray scattering.

Fibrin is an elastomeric protein forming highly extensible fiber networks that provide the scaffold of blood clots. Here we reveal the molecular mechanisms that explain the large extensibility of fibrin networks by performing in situ small angle X-ray scattering measurements while applying a shear deformation. We simultaneously measure shear-induced alignment of the fibers and changes in their axially ordered molecular packing structure.

Poroelasticity of (bio)polymer networks during compression: theory and experiment.

Soft living tissues like cartilage can be considered as biphasic materials comprising a fibrous complex biopolymer network and a viscous background liquid. Here, we show by a combination of experiment and theoretical analysis that both the hydraulic permeability and the elastic properties of (bio)polymer networks can be determined with simple ramp compression experiments in a commercial rheometer. In our approximate closed-form solution of the poroelastic equations of motion, we find the normal force response during compression as a combination of network stress and fluid pressure.

Automated Tracking of Biopolymer Growth and Network Deformation with TSOAX.

Studies of how individual semi-flexible biopolymers and their network assemblies change over time reveal dynamical and mechanical properties important to the understanding of their function in tissues and living cells. Automatic tracking of biopolymer networks from fluorescence microscopy time-lapse sequences facilitates such quantitative studies. We present an open source software tool that combines a global and local correspondence algorithm to track biopolymer networks in 2D and 3D, using stretching open active contours.

The Influence of Radiotherapy on the Mechanical Properties of Silicone Breast Implants.

Background: Silicone breast implants have been used for decades for cosmetic breast augmentation or reconstruction after mastectomy. In selected cases, postmastectomy adjuvant radiotherapy is given with the breast implants in situ. Previous clinical studies have shown that radiotherapy may lead to complications such as capsular contracture and infection and that removal of the implant may be required.

Normal stresses in semiflexible polymer hydrogels.

Biopolymer gels such as fibrin and collagen networks are known to develop tensile axial stress when subject to torsion. This negative normal stress is opposite to the classical Poynting effect observed for most elastic solids including synthetic polymer gels, where torsion provokes a positive normal stress. As shown recently, this anomalous behavior in fibrin gels depends on the open, porous network structure of biopolymer gels, which facilitates interstitial fluid flow during shear and can be described by a phenomenological two-fluid model with viscous coupling between network and solvent.

Observation of Ultrafast Vibrational Energy Transfer in Fibrinogen and Fibrin Fibers.

We study the secondary structure of the blood protein fibrinogen using two-dimensional infrared spectroscopy. With this technique, we identify the amide I' vibrational modes of the antiparallel β-sheets and turns of fibrinogen. We observe ultrafast energy flow among these amide I' vibrational modes with a time constant of ∼7 ps.

Programming the mechanics of cohesive fiber networks by compression.

Fibrous networks are ideal functional materials since they provide mechanical rigidity at low weight. Here, we demonstrate that fibrous networks of the blood clotting protein fibrin undergo a strong and irreversible increase in their mechanical rigidity in response to uniaxial compression. This rigidification can be precisely controlled by the level of applied compressive strain, providing a means to program the network rigidity without having to change its composition.

Buffers Strongly Modulate Fibrin Self-Assembly into Fibrous Networks.

Fibrin is a plasma protein with a central role in blood clotting and wound repair. Upon vascular injury, fibrin forms resilient fibrillar networks (clots) via a multistep self-assembly process, from monomers, to double-stranded protofibrils, to a branched network of thick fibers. In vitro, fibrin self-assembly is sensitive to physicochemical conditions like the solution pH and ionic strength, which tune the strength of the noncovalent driving forces.

Porosity Governs Normal Stresses in Polymer Gels.

When sheared, most elastic solids including metals, rubbers, and polymer gels dilate perpendicularly to the shear plane. This behavior, known as the Poynting effect, is characterized by a positive normal stress. Surprisingly, fibrous biopolymer gels exhibit a negative normal stress under shear.

Fibrin structural and diffusional analysis suggests that fibers are permeable to solute transport.

Unlabelled: Fibrin hydrogels are promising carrier materials in tissue engineering. They are biocompatible and easy to prepare, they can bind growth factors and they can be prepared from a patient's own blood. While fibrin structure and mechanics have been extensively studied, not much is known about the relation between structure and diffusivity of solutes within the network.

Fibrin Networks Support Recurring Mechanical Loads by Adapting their Structure across Multiple Scales.

Tissues and cells sustain recurring mechanical loads that span a wide range of loading amplitudes and timescales as a consequence of exposure to blood flow, muscle activity, and external impact. Both tissues and cells derive their mechanical strength from fibrous protein scaffolds, which typically have a complex hierarchical structure. In this study, we focus on a prototypical hierarchical biomaterial, fibrin, which is one of the most resilient naturally occurring biopolymers and forms the structural scaffold of blood clots.