Mechanical Compression Creates a Quiescent Muscle Stem Cell Niche

Skeletal muscles can regenerate throughout life time from resident Pax7-expressing (Pax7+) muscle stem cells (MuSCs). Pax7+ MuSCs are normally quiescent and localized at a niche in which they are attached to the extracellular matrix basally and compressed against the myofiber apically. Upon muscle injury, MuSCs lose apical contact with the myofiber and re-enter cell cycle to initiate regeneration. Prior studies on the physical niche of MuSCs focused on basal elasticity, and significance of the apical force exerted on MuSCs remains unaddressed. Here we simulate MuSCs' mechanical environment in vivo by applying physical compression to MuSCs' apical surface. We demonstrate that compression drives activated MuSCs back to a quiescent stem cell state, even when seeded on different basal elasticities. By mathematical modeling and manipulating cell tension, we conclude that low overall tension combined with high edge tension generated by compression lead to MuSC quiescence. We further show that apical compression results in up-regulation of Notch downstream genes, accompanied by increased levels of nuclear Notch. The compression-induced nuclear Notch is ligand-independent, as it does not require the canonical S2-cleavage of Notch by ADAM10/17. Our results fill the knowledge gap on the role of apical tension for MuSC fate. Implications to how stem cell fate and activity are interlocked with the mechanical integrity of its resident tissue are discussed.

En route to dynamic life processes by SNARE-mediated fusion of polymer and hybrid membranes

A variety of artificial cells springs from the functionalization of liposomes with proteins. However, these models suffer from low durability without repair and replenishment mechanisms, which can be partly addressed by replacing the lipids with polymers. Yet natural membranes are also dynamically remodeled in multiple cellular processes. Here, we show that synthetic amphiphile membranes also undergo fusion, mediated by the protein machinery for synaptic secretion. We integrated fusogenic SNAREs in polymer and hybrid vesicles and observed efficient membrane and content mixing. We determined bending rigidity and pore edge tension as key parameters for fusion and described its plausible progression through cryo-EM snapshots. These findings demonstrate that dynamic membrane phenomena can be reconstituted in synthetic materials, thereby providing new tools for the assembly of synthetic protocells.

To close or to collapse: the role of charges on membrane stability upon pore formation

Resealing of membrane pores is crucial for cell survival. We study membrane surface charge and medium composition as defining regulators of membrane stability. Pores are generated by electric field or detergents. Giant vesicles composed of zwitterionic and negatively charged lipids mixed at varying ratios are subjected to a single strong electric pulse. Charged vesicles are prone to catastrophic collapse transforming them into tubular structures. The spectrum of destabilization responses includes the generation of long-living submicroscopic pores and partial vesicle bursting. The origin of these phenomena is related to the membrane edge tension, which governs pore closure. This edge tension significantly decreases as a function of the fraction of charged lipids. Destabilization of charged vesicles upon pore formation is universal – it is also observed with other poration stimuli. Disruption propensity is enhanced for membranes made of lipids with higher degree of unsaturation. It can be reversed by screening membrane charge in the presence of calcium ions. We interpret the observed findings in light of theories of stability and curvature generation and discuss mechanisms acting in cells to prevent total membrane collapse upon poration. Enhanced membrane stability is crucial for the success of electroporation-based technologies for cancer treatment and gene transfer.

Suture Edge Tension Control Technologies for Scar Improvement

Mechanotherapy of postoperative scarring is considered an effective measure to prevent pathological scars. Tension increases suture line enlargement, opening the way to infection. Several options have been proposed since decades and are currently used in practice, from adhesive sutures to adhesive dressings, reapproximation devices, and postoperative negative pressure. Closed incision negative pressure therapy (ciNPT) was recently proposed in at-risk patients, showing a significant difference in prevention of infection. These technologies offer a double effect of mechanical stabilization and aspiration of exudates and have recently been extended to different clinical indications. This chapter describes the recently developed technologies to diminish scar enlargement on a suture line and to prevent infection after extensive surgical procedures in thoracic, abdominal, plastic and orthopedic surgery.

A three-dimensional elastoplastic analysis of mixed-mode KI/KII around the crack front

Engineering problems that involve fatigue crack growth and fracture frequently can be studied by taking into account only mode-I features. However, many important problems that involve combined mode I and II loadings cannot be properly analyzed by a pure mode-I approach, which in particular may not be sufficient to estimate fracture toughness for practical purposes in such cases. Such mixed-mode problems involve crack orientation and/or load conditions that lead to combined local Stress Intensity Factors (SIFs) KI/KII around the crack front. Using multiaxial crack tip condition characterized by the crack inclination angle βin a mixed-mode KI/KII modified single edge tension SE(T) specimen, such mixed-mode effects on plastic zone shapes, volumes and plastic work UPL are taken into account to evaluate problems that involve fatigue and fracture.