The viscoelastic living matter from biomolecular condensates to tissues: Comment on "viscoelastic mechanics of living cells" by Zhou et al.

None.

Emergent mechanics of a networked multivalent protein condensate.

Multivalent proteins can form membraneless condensates in cells by liquid-liquid phase separation, and significant efforts have been made to study their biochemical properties. Here, we demonstrate the emergent mechanics of a functional multivalent condensate reconstituted with six postsynaptic density proteins, using atomic-force-microscopy-based mesoscale rheology and quantitative fluorescence measurements. The measured relaxation modulus and protein mobility reveal that the majority (80%) of the proteins in the condensate are mobile and diffuse through a dynamically cross-linked network made of the remaining (20%) non-mobile scaffold proteins.

Integrin αvβ6 mediates the effects of age-related decreases in matrix stiffness on Tenon's fibroblast activation and bleb scarring in glaucoma.

Glaucoma, including primary open-angle glaucoma (POAG) and primary angle-closure glaucoma, leads to optic nerve injury and visual field loss, often necessitating surgical intervention to lower intraocular pressure (IOP). Trabeculectomy, the most common glaucoma surgery, could fail due to excessive scarring of the filtering bleb, driven by the hyperproliferation of human Tenon's fibroblasts (HTFs). Herein, the impact of aging on matrix stiffness in Tenon's capsule tissue, the role of extracellular matrix (ECM) stiffness in the phenotypic transformation of HTFs, and the regulatory function of integrin alphavbeta6 (αvβ6) were investigated.

Regulatory Effects of the Wnt7b/β-Catenin/MMP-2 Signaling Pathway on Scleral Stiffness in Guinea Pigs With Form-Deprivation Myopia.

Purpose: The development and progression of myopia are influenced by the Wnt7b/β-catenin signaling pathway. This study investigated the specific impacts of this pathway on the biomechanical properties of the sclera by altering the expression of matrix metalloproteinase-2 (MMP-2) to regulate type I collagen (collagen I) levels.

Methods: We examined the effects of the Wnt7b/β-catenin signaling pathway and MMP-2 on human fetal scleral fibroblasts (HFSFs) and the sclera of guinea pigs with form-deprivation myopia (FDM).

TRPML1 ion channel promotes HepaRG cell differentiation under simulated microgravity conditions.

Stem cell differentiation must be regulated by intricate and complex interactions between cells and their surrounding environment, ensuring normal organ and tissue morphology such as the liver. Though it is well acknowledged that microgravity provides necessary mechanical force signals for cell fate, how microgravity affects growth, differentiation, and communication is still largely unknown due to the lack of real experimental scenarios and reproducibility tools. Here, Rotating Flat Chamber (RFC) was used to simulate ground-based microgravity effects to study how microgravity effects affect the differentiation of HepaRG (hepatic progenitor cells) cells.

Cavity oscillation drives pattern formation in early mammalian embryos.

During the second cell fate in mouse embryos, the inner cell mass (ICM) segregates into the spatially distinct epiblast (EPI) and primitive endoderm (PrE) layers. The mechanism driving this pattern formation, however, remains unresolved. Here, we report that, concomitant with the segregation process of EPI/PrE precursors starting from mid-blastocyst, the blastocyst cavity begins to oscillate cyclically with rapid contraction yet slow expansion, triggering a phase transition in the ICM to a fluid-like state.

Visible light-responsive hydrogels for cellular dynamics and spatiotemporal viscoelastic regulation.

Viscoelastic heterogeneity of matrices plays a pivotal role in cancer cell spreading, migration, and metastasis. However, the creation of viscoelastic platforms with spatial-temporal regulation is hindered by cytotoxicity and short regulation durations. Our research presents a dual mechanism for stress relaxation regulation- both intrinsic and responsive- by incorporating Schiff base bonds and a visible light-responsive thiuram disulfide (TDS) moiety into the hydrogel.

Sub-Nanogram Resolution Measurement of Inertial Mass and Density Using Magnetic-Field-Guided Bubble Microthruster.

Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble-driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles.

Avalanches and Extreme Value Statistics of a Mesoscale Moving Contact Line.

We report direct atomic force microscopy measurements of pinning-depinning dynamics of a circular moving contact line (CL) over the rough surface of a micron-sized vertical hanging glass fiber, which intersects a liquid-air interface. The measured capillary force acting on the CL exhibits sawtoothlike fluctuations, with a linear accumulation of force of slope k (stick) followed by a sharp release of force δf, which is proportional to the CL slip length. From a thorough analysis of a large volume of the stick-slip events, we find that the local maximal force F_{c} needed for CL depinning follows the extreme value statistics and the measured δf follows the avalanche dynamics with a power law distribution in good agreement with the Alessandro-Beatrice-Bertotti-Montorsi (ABBM) model.

Manipulation of Contact Angle Hysteresis at Electrified Ionic Liquid-Solid Interfaces.

Room-temperature ionic liquids (RTILs) are intriguing fluids that have drawn much attention in applications ranging from tribology and catalysis to energy storage. With strong electrostatic interaction between ions, their interfacial behaviors can be modulated by controlling energetics of the electrified interface. In this work, we report atomic-force-microscope measurements of contact angle hysteresis (CAH) of a circular contact line formed on a micron-sized fiber, which is coated with a thin layer of conductive film and intersects an RTIL-air interface.

Soft Wetting: Droplet Receding Contact Angles on Soft Superhydrophobic Surfaces.

Despite intensive investigations on the droplet receding contact angle on superhydrophobic surfaces, i.e., a key parameter characterizing surface wettability and adhesion, the quantitative correlation between the surface structure mechanical properties (softness) and the droplet receding contact angles remains vague.

Switch of cell migration modes orchestrated by changes of three-dimensional lamellipodium structure and intracellular diffusion.

Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium.

Crossover behavior in stress relaxations of poroelastic and viscoelastic dominant hydrogels.

The mechanical response and relaxation behavior of hydrogels are crucial to their diverse functions and applications. However, understanding how stress relaxation depends on the material properties of hydrogels and accurately modeling relaxation behavior at multiple time scales remains a challenge for soft matter mechanics and soft material design. While a crossover phenomenon in stress relaxation has been observed in hydrogels, living cells, and tissues, little is known about how the crossover behavior and characteristic crossover time depend on material properties.

Cellular proteins act as surfactants to control the interfacial behavior and function of biological condensates.

Interfacial tension governs the behaviors and physiological functions of multiple biological condensates during diverse biological processes. Little is known about whether there are cellular surfactant factors that regulate the interfacial tension and functions of biological condensates within physiological environments. TFEB, a master transcription factor that controls expression of autophagic-lysosomal genes, assembles into transcriptional condensates to control the autophagy-lysosome pathway (ALP).

Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.

The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell-ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness.

Heterogeneous Nanostructures Cause Anomalous Diffusion in Lipid Monolayers.

The diffusion and mobility in biomembranes are crucial for various cell functions; however, the mechanisms involved in such processes remain ambiguous due to the complex membrane structures. Herein, we investigate how the heterogeneous nanostructures cause anomalous diffusion in dipalmitoylphosphatidylcholine (DPPC) monolayers. By identifying the existence of condensed nanodomains and clarifying their impact, our findings renew the understanding of the hydrodynamic description and the statistical feature of the diffusion in the monolayers.

Multimodal Bubble Microrobot Near an Air-Water Interface.

The development of multifunctional and robust swimming microrobots working at the free air-liquid interface has encountered challenge as new manipulation strategies are needed to overcome the complicated interfacial restrictions. Here, flexible but reliable mechanisms are shown that achieve a remote-control bubble microrobot with multiple working modes and high maneuverability by the assistance of a soft air-liquid interface. This bubble microrobot is developed from a hollow Janus microsphere (JM) regulated by a magnetic field, which can implement switchable working modes like pusher, gripper, anchor, and sweeper.

Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway.

Very little is known about how the material properties of protein condensates assembled via liquid-liquid phase separation (LLPS) are maintained and affect physiological functions. Here we show that liquid-like condensates of the transcription factor TFEB exhibit low fusion propensity in vitro and in living cells. We directly measured the attraction force between droplets, and we characterized the interfacial tension, viscosity, and elasticity of TFEB condensates.

Programmable light-driven swimming actuators via wavelength signal switching.

Light-driven swimming actuators with different motion modes could lead to many previously unachievable applications. However, controllable navigation often requires focusing light precisely on certain positions of the actuator, which is unfavorable for accurate dynamical operation or in microscale applications. Here, we present a type of programmable swimming actuators that can execute wavelength-dependent multidirectional motions via the Marangoni effect.

Edible Bird's Nest, an Asian Health Food Supplement, Possesses Moisturizing Effect by Regulating Expression of Filaggrin in Skin Keratinocyte.

Edible bird's nest (EBN) has been consumed as a Chinese delicacy for hundreds of years; the functions of which have been proposed to prevent lung disease, strengthen immune response, and restore skin youthfulness. To support the skin function of EBN, the water extract and the enzymatic digest of EBN with enriched digested peptides were tested in cultured keratinocyte, HaCaT cell line. The effects of EBN extract and digest in inducing proteins crucial for skin moisturizing were determined in both and models.

State and Rate Dependent Contact Line Dynamics over an Aging Soft Surface.

We report direct atomic-force-microscope measurements of capillary force hysteresis (CFH) of a circular contact line (CL) formed on a long glass fiber, which is coated with a thin layer of soft polymer film and intersects a water-air interface. The measured CFH shows a distinct overshoot for the depinning of a static CL, and the overshoot amplitude grows logarithmically with both the hold time τ and fiber speed V. A unified model based on the slow growth of a wetting ridge and force-assisted barrier crossing is developed to explain the observed time (or state) and speed (or rate) dependent CL depinning dynamics over an aging soft surface.

Reconstituted Postsynaptic Density as a Molecular Platform for Understanding Synapse Formation and Plasticity.

Synapses are semi-membraneless, protein-dense, sub-micron chemical reaction compartments responsible for signal processing in each and every neuron. Proper formation and dynamic responses to stimulations of synapses, both during development and in adult, are fundamental to functions of mammalian brains, although the molecular basis governing formation and modulation of compartmentalized synaptic assemblies is unclear. Here, we used a biochemical reconstitution approach to show that, both in solution and on supported membrane bilayers, multivalent interaction networks formed by major excitatory postsynaptic density (PSD) scaffold proteins led to formation of PSD-like assemblies via phase separation.

A simple fabricated thickness-based stiffness gradient for cell studies.

In this work, we developed a simple method to fabricate a thickness-based continuous stiffness gradient for biological studies. It was made by glass slides, polydimethylsiloxane (PDMS) pre-polymer, spacer and clips only, without any sophisticated equipment. It is easy to fabricate in any general biological and pharmaceutical laboratories.

Mechanical Characterization of Microengineered Epithelial Cysts by Using Atomic Force Microscopy.

Most organs contain interconnected tubular tissues that are one-cell-thick, polarized epithelial monolayers enclosing a fluid-filled lumen. Such tissue organization plays crucial roles in developmental and normal physiology, and the proper functioning of these tissues depends on their regulation by complex biochemical perturbations and equally important, but poorly understood, mechanical perturbations. In this study, by combining micropatterning techniques and atomic force microscopy, we developed a simple in vitro experimental platform for characterizing the mechanical properties of the MDCK II cyst, the simplest model of lumen-enclosing epithelial monolayers.

Noncontact Viscoelastic Measurement of Polymer Thin Films in a Liquid Medium Using Long-Needle Atomic Force Microscopy.

We report the noncontact measurement of the viscoelastic property of polymer thin films in a liquid medium using frequency-modulation atomic force microscopy with a newly developed long-needle probe. The probe contains a long vertical glass fiber with one end adhered to a cantilever beam and the other end with a sharp tip placed near the liquid-film interface. The nanoscale flow generated by the resonant oscillation of the needle tip provides a precise hydrodynamic force acting on the soft surface of the thin film.