PCP and Septins govern the polarized organization of the actin cytoskeleton during convergent extension.

Convergent extension (CE) requires the coordinated action of the planar cell polarity (PCP) proteins and the actin cytoskeleton, but this relationship remains incompletely understood. For example, PCP signaling orients actomyosin contractions, yet actomyosin is also required for the polarized localization of PCP proteins. Moreover, the actin-regulating Septins play key roles in actin organization and are implicated in PCP and CE in frogs, mice, and fish but execute only a subset of PCP-dependent cell behaviors.

New tools reveal PCP-dependent polarized mechanics in the cortex and cytoplasm of single cells during convergent extension.

Unlabelled: Understanding biomechanics of biological systems is crucial for unraveling complex processes like tissue morphogenesis. However, current methods for studying cellular mechanics are limited by the need for specialized equipment and often provide limited spatiotemporal resolution. Here we introduce two new techniques, Tension by Transverse Fluctuation (TFlux) and microrheology, that overcome these limitations.

Inhibition of ribosome biogenesis in the epidermis is sufficient to trigger organism-wide growth quiescence independently of nutritional status in C. elegans.

Interorgan communication is crucial for multicellular organismal growth, development, and homeostasis. Cell nonautonomous inhibitory cues, which limit tissue-specific growth alterations, are not well characterized due to cell ablation approach limitations. In this study, we employed the auxin-inducible degradation system in C.

Convergent extension requires adhesion-dependent biomechanical integration of cell crawling and junction contraction.

Convergent extension (CE) is an evolutionarily conserved collective cell movement that elongates several organ systems during development. Studies have revealed two distinct cellular mechanisms, one based on cell crawling and the other on junction contraction. Whether these two behaviors collaborate is unclear.

ARVCF catenin controls force production during vertebrate convergent extension.

The design of an animal's body plan is encoded in the genome, and the execution of this program is a mechanical progression involving coordinated movement of proteins, cells, and whole tissues. Thus, a challenge to understanding morphogenesis is connecting events that occur across various length scales. Here, we describe how a poorly characterized adhesion effector, Arvcf catenin, controls Xenopus head-to-tail axis extension.

Mechanical heterogeneity along single cell-cell junctions is driven by lateral clustering of cadherins during vertebrate axis elongation.

Morphogenesis is governed by the interplay of molecular signals and mechanical forces across multiple length scales. The last decade has seen tremendous advances in our understanding of the dynamics of protein localization and turnover at subcellular length scales, and at the other end of the spectrum, of mechanics at tissue-level length scales. Integrating the two remains a challenge, however, because we lack a detailed understanding of the subcellular patterns of mechanical properties of cells within tissues.

Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells.

Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo.

May the force be with you.

Understanding the coordination of the forces generated in embryos by two processes, convergent extension and convergent thickening, is key to understanding how a hollow sphere of cells develops into an elongated embryo.

Nanotopography regulates motor neuron differentiation of human pluripotent stem cells.

The regulation of human pluripotent stem cell (hPSC) behaviors has been mainly studied through exploration of biochemical factors. However, the current directed differentiation protocols for hPSCs that completely rely on biochemical factors remain suboptimal. It has recently become evident that coexisting biophysical signals in the stem cell microenvironment, including nanotopographic cues, can provide potent regulatory signals to mediate adult stem cell behaviors, including self-renewal and differentiation.

Effects of substrate stiffness and actomyosin contractility on coupling between force transmission and vinculin-paxillin recruitment at single focal adhesions.

Focal adhesions (FAs) regulate force transfer between the cytoskeleton and ECM-integrin complexes. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin's active conformation to promote force transfer.

Mechanosensitive subcellular rheostasis drives emergent single-cell mechanical homeostasis.

Mechanical homeostasis-a fundamental process by which cells maintain stable states under environmental perturbations-is regulated by two subcellular mechanotransducers: cytoskeleton tension and integrin-mediated focal adhesions (FAs). Here, we show that single-cell mechanical homeostasis is collectively driven by the distinct, graduated dynamics (rheostasis) of subcellular cytoskeleton tension and FAs. Such rheostasis involves a mechanosensitive pattern wherein ground states of cytoskeleton tension and FA determine their distinct reactive paths through either relaxation or reinforcement.

Desktop aligner for fabrication of multilayer microfluidic devices.

Multilayer assembly is a commonly used technique to construct multilayer polydimethylsiloxane (PDMS)-based microfluidic devices with complex 3D architecture and connectivity for large-scale microfluidic integration. Accurate alignment of structure features on different PDMS layers before their permanent bonding is critical in determining the yield and quality of assembled multilayer microfluidic devices. Herein, we report a custom-built desktop aligner capable of both local and global alignments of PDMS layers covering a broad size range.

Age-Associated Increase in Skin Fibroblast-Derived Prostaglandin E2 Contributes to Reduced Collagen Levels in Elderly Human Skin.

Production of type I collagen declines during aging, leading to skin thinning and impaired function. Prostaglandin E2 (PGE2) is a pleiotropic lipid mediator that is synthesized from arachidonic acid by the sequential actions of cyclooxygenases (COX) and PGE synthases (PTGES). PGE2 inhibits collagen production by fibroblasts in vitro.

Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells.

Our understanding of the intrinsic mechanosensitive properties of human pluripotent stem cells (hPSCs), in particular the effects that the physical microenvironment has on their differentiation, remains elusive. Here, we show that neural induction and caudalization of hPSCs can be accelerated by using a synthetic microengineered substrate system consisting of poly(dimethylsiloxane) micropost arrays (PMAs) with tunable mechanical rigidities. The purity and yield of functional motor neurons derived from hPSCs within 23 days of culture using soft PMAs were improved more than fourfold and tenfold, respectively, compared with coverslips or rigid PMAs.

Nanoroughened surfaces for efficient capture of circulating tumor cells without using capture antibodies.

Circulating tumor cells (CTCs) detached from both primary and metastatic lesions represent a potential alternative to invasive biopsies as a source of tumor tissue for the detection, characterization and monitoring of cancers. Here we report a simple yet effective strategy for capturing CTCs without using capture antibodies. Our method uniquely utilized the differential adhesion preference of cancer cells to nanorough surfaces when compared to normal blood cells and thus did not depend on their physical size or surface protein expression, a significant advantage as compared to other existing CTC capture techniques.

Live-cell subcellular measurement of cell stiffness using a microengineered stretchable micropost array membrane.

Forces are increasingly recognized as major regulators of cell structure and function, and the mechanical properties of cells, such as cell stiffness, are essential to the mechanisms by which cells sense forces, transmit them to the cell interior or to other cells, and transduce them into chemical signals that impact a spectrum of cellular responses. Here we reported a new whole-cell cell stiffness measurement technique with a subcellular spatial resolution. This technique was based on a novel cell stretching device that allowed for quantitative control and real-time measurements of mechanical stimuli and cellular biomechanical responses.

Microengineered synthetic cellular microenvironment for stem cells.

Stem cells possess the ability of self-renewal and differentiation into specific cell types. Therefore, stem cells have great potentials in fundamental biology studies and clinical applications. The most urgent desire for stem cell research is to generate appropriate artificial stem cell culture system, which can mimic the dynamic complexity and precise regulation of the in vivo biochemical and biomechanical signals, to regulate and direct stem cell behaviors.

Nanotopography influences adhesion, spreading, and self-renewal of human embryonic stem cells.

Human embryonic stem cells (hESCs) have great potentials for future cell-based therapeutics. However, their mechanosensitivity to biophysical signals from the cellular microenvironment is not well characterized. Here we introduced an effective microfabrication strategy for accurate control and patterning of nanoroughness on glass surfaces.

A silicone-based stretchable micropost array membrane for monitoring live-cell subcellular cytoskeletal response.

External forces are increasingly recognized as major regulators of cellular structure and function, yet the underlying mechanism by which cells sense forces and transduce them into intracellular biochemical signals and behavioral responses ('mechanotransduction') is largely undetermined. To aid in the mechanistic study of mechanotransduction, herein we devised a cell stretching device that allowed for quantitative control and real-time measurement of mechanical stimuli and cellular biomechanical responses. Our strategy involved a microfabricated array of silicone elastomeric microposts integrated onto a stretchable elastomeric membrane.

Synergistic regulation of cell function by matrix rigidity and adhesive pattern.

Cell-extracellular matrix (ECM) interactions play a critical role in regulating cellular behaviors. Recent studies of cell-ECM interactions have mainly focused on the actomyosin based and adhesion mediated mechanosensing pathways to understand how individual mechanical signals in the cell microenvironment, such as matrix rigidity and adhesive ECM pattern, are sensed by the cell and further trigger downstream intracellular signaling cascades and cellular responses. However, synergistic and collective regulation of cellular behaviors by matrix rigidity and adhesive ECM pattern are still elusive and largely uncharacterized.