A5013577650- Cellular Mechanics and Interactions
- Asthma and respiratory diseases
- 3D Printing in Biomedical Research
- Force Microscopy Techniques and Applications
- Osteoarthritis Treatment and Mechanisms
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Blood properties and coagulation
- IL-33, ST2, and ILC Pathways
- Total Knee Arthroplasty Outcomes
- Lower Extremity Biomechanics and Pathologies
- Cancer Cells and Metastasis
- Cell Adhesion Molecules Research
- Respiratory Support and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Tendon Structure and Treatment
- Microfluidic and Bio-sensing Technologies
- Angiogenesis and VEGF in Cancer
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Renal Diseases and Glomerulopathies
- Receptor Mechanisms and Signaling
- Renal and related cancers
Beth Israel Deaconess Medical Center
2015-2024
Center for Vascular Biology Research
2015-2024
Harvard University
2015-2024
Anna University, Chennai
2024
Muscat College
2023
Hadassah Medical Center
2015-2021
Beth Israel Deaconess Hospital
2013
Columbia University
2001-2005
Every adherent eukaryotic cell exerts appreciable traction forces upon its substrate. Moreover, every resident within the heart, great vessels, bladder, gut or lung routinely experiences large periodic stretches. As an acute response to such stretches cytoskeleton can stiffen, increase and reinforce, as reported by some, soften fluidize, more recently our laboratory, but in any given circumstance it remains unknown which might prevail why. Using a novel nanotechnology, we show here that...
Macrophages serve to maintain organ homeostasis in response challenges from injury, inflammation, malignancy, particulate exposure, or infection. Until now, receptor ligation has been understood as being the central mechanism that regulates macrophage function. Using macrophages of different origins and species, we report elasticity is a major determinant innate Macrophage modulated not only by classical biologic activators such LPS IFN-γ, but an equal extent substrate rigidity stretch....
ABSTRACT The actin and intermediate filament cytoskeletons contribute to numerous cellular processes, including morphogenesis, cytokinesis migration. These two cytoskeletal systems associate with each other, but the underlying mechanisms of this interaction are incompletely understood. Here, we show that inactivation vimentin leads increased stress fiber assembly contractility, consequent elevation myosin light chain phosphorylation stabilization tropomyosin-4.2 (see Geeves et al., 2015)....
The objective of the current study was to measure friction coefficient simultaneously with interstitial fluid load support in bovine articular cartilage, while sliding against glass under a constant load. Ten visually normal 6-mm-diameter cartilage plugs harvested from humeral head four shoulder joints (ages 2-4 months) were tested custom device reciprocating linear motion (range translation +/-2 mm; velocity 1 mm/s), subjected 4.5 N frictional found increase time minimum value mu...
A hallmark of many, sometimes life-threatening, inflammatory diseases and disorders is vascular leakage. The extent severity leakage broadly mediated by the integrity endothelial cell (EC) monolayer, which in turn governed three major interactions: cell-cell cell-substrate contacts, soluble mediators, biomechanical forces. potentially critical but essentially uninvestigated component mediating these interactions stiffness substrate to monolayer adherent. Accordingly, we investigated...
Adhesion and morphogenesis of many non-muscle cells are guided by contractile actomyosin bundles called ventral stress fibers. While it is well established that fibers mechanosensitive structures, physical mechanisms which they assemble, align, mature have remained elusive. Here we show arcs, serve as precursors for fibers, undergo lateral fusion during their centripetal flow to form thick apply tension focal adhesions at ends. Importantly, this myosin II-derived force inhibits vectorial...
Endothelial cell alignment along the direction of laminar fluid flow is widely understood to be a defining morphological feature vascular homeostasis. While role associated signaling and structural events have been well studied, intercellular stresses under shear remained ill-defined these in process has obscure. To fill this gap, we report here tractions as complete in-plane stress fields measured within human umbilical vein endothelial (HUVEC) monolayer subjected steady 1 Pa. Tractions,...
Significance In this study, we examine how proteins that cross-link actin filaments control certain biophysical aspects of living cells. We studied α-actinin-4 (ACTN4) a dimeric rod-shaped homodimer, particular interest because mutations in its binding domain cause human disease characterized by dysfunction the kidney’s glomeruli; however, mechanical impact such are unknown. find disease-causing K255E mutation ACTN4 leads to change cellular properties, increasing affinity for increases...
Cells resident in certain hollow organs are subjected routinely to large transient stretches, including every adherent cell lungs, heart, great vessels, gut, and bladder. We have shown recently that response a stretch the eukaryotic promptly fluidizes then gradually resolidifies, but mechanism is not yet understood.In isolated human bladder smooth muscle cell, here we applied 10% while measuring traction forces, elastic modulus, F-actin imaging F-actin/G-actin ratio. Immediately after...
Primary open-angle glaucoma is associated with elevated intraocular pressure, which in turn believed to result from impaired outflow of aqueous humour. Aqueous humour passes mainly through the trabecular meshwork (TM) and then pores formed endothelium Schlemm's canal (SC), experiences a basal-to-apical pressure gradient. This gradient dramatically deforms SC endothelial cell potentially contributes formation those pores. However, mechanical properties are poorly defined. Using optical...
In the normal lung, breathing and deep inspirations potently antagonize bronchoconstriction, but in asthmatic lung this salutary effect is substantially attenuated or even reversed. To explain these findings, prevailing hypothesis focuses on contracting airway smooth muscle posits a nonlinear dynamic interaction between actomyosin binding tethering forces imposed by tidally expanding parenchyma.This has never been tested directly bronchial embedded within intraparenchymal airways. Our...
Therapeutic ultrasound is widely employed in clinical applications but its mechanism of action remains unclear. Here we report prompt fluidization a cell and dramatic acceleration remodeling dynamics when exposed to low intensity ultrasound. These physical changes are caused by very small strains (10−5) at ultrasonic frequencies (106 Hz), closely analogous those relatively large (10−1) physiological (100 Hz). Moreover, these reminiscent rejuvenation aging phenomena that well-established...
The spreading area of cells has been shown to play a central role in the determination cell fate and tissue morphogenesis; however, clear understanding how spread is determined still lacking. observation that force generally increase with substrate rigidity suggests dictated mechanically, by means force-balance between substrate. A simple mechanical model, corroborated experimental measurements presented analyze temporal balance during spreading. modeled as thin elastic disc actively pulled...
Using cellular contractile force as the target, we report a new high-throughput screening technology.
Abstract For an airway or a blood vessel to narrow, there must be connected path that links the smooth muscle (SM) cells with each other, and transmits forces around organ, causing it constrict. Currently, we know very little about mechanisms regulate force transmission pathways in multicellular SM ensemble. Here, used extracellular matrix (ECM) micropatterning study two-cell ensemble of cells. Using two-SM cell ensemble, demonstrate (a) ECM stiffness acts as switch regulates whether is...
It has been well established that articular cartilage is compositionally and mechanically inhomogeneous through its depth. To what extent this structural inhomogeneity a prerequisite for appropriate function integrity not understood. The first hypothesis to be tested in study was the depth-dependent of acts maximize interstitial fluid load support at surface, provide efficient frictional wear properties. second produces more homogeneous state elastic stress matrix than would achieved with...
Structure and function of the adherent cell depend in a crucial way on its microenvironment, including stiffness substrate. It is often asserted that substrate thickness (as opposed to stiffness) plays negligible role therefore may be considered semi-infinite. This assertion has been recently challenged, but characteristic length scale consider this regard poorly understood. We show here lateral size. As approaches dimension cell, apparent amplified levels much greater than intrinsic change...
Rationale: An asthma-like airway phenotype has been described in people with cystic fibrosis (CF). Whether these findings are directly caused by loss of CF transmembrane conductance regulator (CFTR) function or secondary to chronic infection and/or inflammation difficult determine.Objectives: Airway contractility is primarily determined smooth muscle. We tested the hypothesis that CFTR expressed muscle and affects contractility.Methods: Newborn pigs, both wild type (before onset...