The role of cell-matrix adhesion and cell migration in breast tumor growth and progression.

During breast cancer progression, there is typically increased collagen deposition resulting in elevated extracellular matrix rigidity. This results in changes to cell-matrix adhesion and cell migration, impacting processes such as the epithelial-mesenchymal transition (EMT) and metastasis. We aim to investigate the roles of cell-matrix adhesion and cell migration on breast tumor growth and progression by studying the impacts of different types of extracellular matrices and their rigidities.

Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface.

Biochemical signaling and mechano-transduction are both critical in regulating stem cell fate. How crosstalk between mechanical and biochemical cues influences embryonic development, however, is not extensively investigated. Using a comparative study of focal adhesion constituents between mouse embryonic stem cell (mESC) and their differentiated counterparts, we find while zyxin is lowly expressed in mESCs, its levels increase dramatically during early differentiation.

A chemotaxis model to explain WHIM neutrophil accumulation in the bone marrow of WHIM mouse model.

Neutrophils are essential immune cells that defend the host against pathogenic microbial agents. Neutrophils are produced in the bone marrow and are retained there through CXCR4-CXCL12 signaling. However, patients with the Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome are prone to infections due to increased accumulation of neutrophils in the bone marrow leading to low numbers of circulating neutrophils.

Anisotropic traction stresses and focal adhesion polarization mediates topography-induced cell elongation.

Cell elongation and differentiation has been shown to be modulated by topographical cues provided by grating substratum. However, little is known about the mechanisms and forces involved in the grating-induced cell elongation, due to the difficulty in fabricating soft elastic gels that allow 3-dimensional (3D) cell traction stress measurements. In this paper, we present a method to fabricate soft elastic polyacrylamide grating substrates, using an imprinted polyethylene terephthalate mould, for 3D cell traction stress measurements.

Cell-Cell Adhesion and Cortical Actin Bending Govern Cell Elongation on Negatively Curved Substrates.

Physiologically, cells experience and respond to a variety of mechanical stimuli such as rigidity and topography of the extracellular matrix. However, little is known about the effects of substrate curvature on cell behavior. We developed a novel, to our knowledge, method to fabricate cell culture substrates with semicylindrical grooves of negative curvatures (radius of curvature, R = 20-100 μm).

Epithelial Monolayers Coalesce on a Viscoelastic Substrate through Redistribution of Vinculin.

The mechanical properties of the microenvironment play a large role in influencing cellular behavior. In particular, the tradeoff between substrate viscosity and elasticity on collective cell migration by adherent cells is highly physiologically relevant, but remains poorly understood. To investigate the specific effects of viscous substrates, we plated epithelial monolayers onto polydimethylsiloxane substrata with a range of viscosities and elasticities.

MEKK1-dependent phosphorylation of calponin-3 tunes cell contractility.

MEKK1 (also known as MAP3K1), which plays a major role in MAPK signaling, has been implicated in mechanical processes in cells, such as migration. Here, we identify the actin-binding protein calponin-3 as a new MEKK1 substrate in the signaling that regulates actomyosin-based cellular contractility. MEKK1 colocalizes with calponin-3 at the actin cytoskeleton and phosphorylates it, leading to an increase in the cell-generated traction stress.

Traction stress analysis and modeling reveal that amoeboid migration in confined spaces is accompanied by expansive forces and requires the structural integrity of the membrane-cortex interactions.

Leukocytes and tumor cells migrate via rapid shape changes in an amoeboid-like manner, distinct from mesenchymal cells such as fibroblasts. However, the mechanisms of how rapid shape changes are caused and how they lead to migration in the amoeboid mode are still unclear. In this study, we confined differentiated human promyelocytic leukemia cells between opposing surfaces of two pieces of polyacrylamide gels and characterized the mechanics of fibronectin-dependent mesenchymal versus fibronectin-independent amoeboid migration.

Loss of p53 enhances NF-κB-dependent lamellipodia formation.

Tumor suppressor p53 prevents tumorigenesis and tumor growth by suppressing the activation of several transcription factors, including nuclear factor-κB (NF-κB) and STAT3. On the other hand, p53 stimulates actin cytoskeleton remodeling and integrin-related signaling cascades. Here, we examined the p53-mediated link between regulation of the actin cytoskeleton and activation of NF-κB and STAT3 in MCF-7 cells and mouse embryonic fibroblasts (MEFs).

Cellular response to substrate rigidity is governed by either stress or strain.

Cells sense the rigidity of their substrate; however, little is known about the physical variables that determine their response to this rigidity. Here, we report traction stress measurements carried out using fibroblasts on polyacrylamide gels with Young's moduli ranging from 6 to 110 kPa. We prepared the substrates by employing a modified method that involves N-acryloyl-6-aminocaproic acid (ACA).

A three-dimensional random network model of the cytoskeleton and its role in mechanotransduction and nucleus deformation.

We have developed a three-dimensional random network model of the intracellular actin cytoskeleton and have used it to study the role of the cytoskeleton in mechanotransduction and nucleus deformation. We use the model to predict the deformation of the nucleus when mechanical stresses applied on the plasma membrane are propagated through the random cytoskeletal network to the nucleus membrane. We found that our results agree with previous experiments utilizing micropipette pulling.