Haguy Wolfenson

Haguy Wolfenson
Technion - Israel Institute of Technology | technion · Rappaport Faculty of Medicine

PhD

About

69
Publications
8,436
Reads
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2,055
Citations
Citations since 2017
31 Research Items
1494 Citations
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Introduction
I am an Assistant Professor at the Rappaport Faculty of Medicine of the Technion - Israel Institute of Technology. The research in my group focuses on cellular mechanosensing and the effects of the extracellular matrix on cell decisions in health and disease.
Additional affiliations
October 2016 - present
Technion - Israel Institute of Technology
Position
  • Professor (Assistant)
September 2011 - present
Columbia University
Position
  • PostDoc Position
October 2006 - August 2011
Weizmann Institute of Science
Position
  • PhD Student
Education
October 2006 - August 2011
Tel Aviv University
Field of study
  • Biology

Publications

Publications (69)
Preprint
Full-text available
Cells' ability to apply contractile forces to their environment and to sense its mechanical properties (e.g. rigidity) are among their most fundamental features. Yet, the interrelations between contractility and mechanosensing, in particular whether contractile force generation depends on mechanosensing, are not understood. We use theory and extens...
Article
Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied by local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal- and spatial-resolution tracking of contractile forces...
Article
It is increasingly clear that mechanotransduction pathways play important roles in regulating fundamental cellular functions. Of the basic mechanical functions, the determination of cellular morphology is critical. Cells typically use many mechanosensitive steps and different cell states to achieve a polarized shape through repeated testing of the...
Article
To understand how cells form tissues, we need to understand how the tyrosine kinases are involved in controlling cell mechanics, whether they act directly as parts of mechanosensing machines or indirectly. Cells test the critical parameter of matrix rigidity by locally contracting ("pinching") matrices and measuring forces, and the depletion of con...
Article
Accurately evaluating cellular forces is critical for studying mechanosensing and mechanotransduction processes, and it necessitates sensitive measurements on the piconewton scale. Here we describe a specialized method that employs elastic polydimethylsiloxane (PDMS) micropillar arrays, which cells can adhere to and bend. The flexibility of the pil...
Article
Full-text available
Primary fibroblasts from patient’s skin biopsies are directly isolated without any alteration in the genome, retaining in culture conditions their endogenous cellular characteristics and biochemical properties. The aim of this study was to identify a distinctive cell phenotype for potential drug evaluation in fibroblasts from Huntington’s Disease (...
Article
Full-text available
Cell-matrix and cell-cell adhesion play important roles in a wide variety of physiological processes, from the single cell level to the large scale, multicellular organization of tissues. Cells actively apply forces to their environment, either extracellular matrix or neighboring cells, as well as sense its biophysical properties. The fluctuations...
Preprint
Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular-matrix. However, force transmission is in itself dependent on fibrillogenesis, and fibronectin fibrils are found in soft embryos where sufficient force cannot be applied, demonstrating that force cannot be the sole initiator of fi...
Preprint
Full-text available
Cell-matrix and cell-cell adhesion play important roles in a wide variety of physiological processes, from the single cell level to the large scale, multicellular organization of tissues. Cells actively apply forces to their environment, either extracellular matrix or neighboring cells, as well as sense its biophysical properties. The fluctuations...
Article
Full-text available
Cancer cells normally grow on soft surfaces due to impaired mechanosensing of the extracellular matrix rigidity. Upon restoration of proper mechanosensing, cancer cells undergo apoptosis on soft surfaces (anoikis) like most normal cells. However, the link between mechanosensing and activation of anoikis is not clear. Here we show that death associa...
Article
Full-text available
Both cell–cell and cell–matrix adhesions are regulated by mechanical signals, but the mechanobiological processes that mediate the cross talk between these structures are poorly understood. Here we show that α-catenin, a mechanosensitive protein that is classically linked with cadherin-based adhesions, associates with and regulates integrin adhesio...
Preprint
Human primary skin fibroblast cells from patients skin biopsies were used previously as a model to study different neurodegenerative diseases, including Huntingtons Disease (HD). These cells are directly isolated from the patients tissue without any alteration in the genome, retaining in culture conditions their endogenous cellular characteristics...
Preprint
Full-text available
Both cell-cell and cell-matrix adhesions are regulated by mechanical signals, but the mechanobiological processes that mediate the crosstalk between these structures are poorly understood. Here we show that α-catenin, a mechanosensitive protein that is classically associated with cadherin-based adhesions, directly interacts with and regulates integ...
Article
Recent studies highlight how stem cells (SCs) perceive and respond to various biomechanical cues from the extracellular niche and neighboring cells. These combined inputs drive certain stem cell behaviors, including cell fate decisions, and may influence aging and disease.
Article
Full-text available
In cancer, two unique and seemingly contradictory behaviors are evident: on the one hand, tumors are typically stiffer than the tissues in which they grow, and this high stiffness promotes their malignant progression; on the other hand, cancer cells are anchorage-independent—namely, they can survive and grow in soft environments that do not support...
Preprint
Full-text available
Stem cells’ (SCs) decision to self-renew or differentiate largely depends on the extracellular environment and elasticity of their niche. A well-described mediator of the mechanotransduction pathway is the co-transcriptional activator Yes-associated protein (YAP), known to shuttle into the nucleus of cells grown on stiff matrices. YAP is also known...
Preprint
Full-text available
The physical interactions of cells with their external environment are critical for their survival and function. These interactions are altered upon epithelial to mesenchymal transition (EMT) as cells switch from relying primarily on cell-cell adhesions to relying on cell-matrix adhesions. Mechanical signals are central to regulating these two type...
Article
Full-text available
It is well recognized that isolated cardiac muscle cells beat in a periodic manner. Recently, evidence indicates that other, non-muscle cells, also perform periodic motions that are either imperceptible under conventional lab microscope lens or practically not easily amenable for analysis of oscillation amplitude, frequency, phase of movement and i...
Article
Full-text available
Tumor cell heterogeneity is primarily dictated by mutational changes, sometimes leading to clones that undergo a metastatic switch. However, little is known about tumor heterogeneity following chemotherapy perturbation. Here we studied the possible involvement of tumor-derived extracellular vesicles, often referred to as tumor-derived microparticle...
Article
Nitric oxide (NO)-dependent signaling and cytotoxic effects are mediated in part via protein S-nitrosylation. The magnitude and duration of S-nitrosylation are governed by the two main thiol reducing systems, the glutathione (GSH) and thioredoxin (Trx) antioxidant systems. In recent years, approaches have been developed to harness the cytotoxic pot...
Article
Mechanisms regulating nuclear organization control fundamental cellular processes, including the cell and chromatin organization. Their disorganization, including aberrant nuclear architecture, has been often implicated in cellular transformation. Here, we identify Lamin A, among proteins essential for nuclear architecture, as SPANX (sperm protein...
Article
Full-text available
Cells’ ability to apply contractile forces to their environment and to sense its mechanical properties (e.g., rigidity) are among their most fundamental features. Yet, the interrelations between contractility and mechanosensing, in particular, whether contractile force generation depends on mechanosensing, are not understood. We use theory and exte...
Article
Full-text available
A common feature of cancer cells is the alteration of kinases and biochemical signalling pathways enabling transformed growth on soft matrices, whereas cytoskeletal protein alterations are thought to be a secondary issue. However, we report here that cancer cells from different tissues can be toggled between transformed and rigidity-dependent growt...
Preprint
Full-text available
Cells’ ability to apply contractile forces to their environment and to sense its mechanical properties (e.g. rigidity) are among their most fundamental features. Yet, the interrelations between contractility and mechanosensing, in particular whether contractile force generation depends on mechanosensing, are not understood. We use theory and extens...
Preprint
Classical soft agar assays indicate that cancer cells do not properly sense the rigidity of their environment, as non-cancer cells typically undergo anoikis under such conditions. However, it is unclear how rigidity sensing activates anoikis. Here, we show that death-associated protein kinase (DAPK1), which is linked to anoikis and correlates with...
Preprint
Full-text available
The major hallmark of cancer cells is uncontrollable growth on soft matrices (transformed growth), which indicates that they have lost the ability to properly sense the rigidity of their surroundings. Recent studies of fibroblasts show that local contractions by cytoskeletal rigidity sensor units block growth on soft surfaces and their depletion ca...
Article
Cell growth depends upon formation of cell-matrix adhesions, but mechanisms detailing the transmission of signals from adhesions to control proliferation are still lacking. Here, we find that the scaffold protein talin undergoes force-induced cleavage in early adhesions to produce the talin rod fragment that is needed for cell cycle progression. Ex...
Article
Epidermal growth factor receptor (EGFR) interacts with integrins during cell spreading and motility, but little is known about the role of EGFR in these mechanosensing processes. Here we show, using two different cell lines, that in serum- and EGF-free conditions, EGFR or HER2 activity increase spreading and rigidity-sensing contractions on rigid,...
Article
Full-text available
During spreading and migration, the leading edges of cells undergo periodic protrusion–retraction cycles. The functional purpose of these cycles is unclear. Here, using submicrometer polydimethylsiloxane pillars as substrates for cell spreading, we show that periodic edge retractions coincide with peak forces produced by local contractile units (CU...
Article
During spreading and migration, the leading edges of many cells undergo periodic protrusion-retraction cycles. The functional purpose of these cycles is unclear. Here, using submicrometer PDMS pillars as substrates for cell spreading, we show that periodic edge retractions coincide with peak forces produced by local contractile units that assemble...
Article
Single molecule nanodot arrays, in which a biomolecule of choice (protein, nucleic acid, etc.) is bound to a metallic nanoparticle on a solid substrate, are becoming an increasingly important tool in the study of biomolecular and cellular interactions. We have developed an on-chip measurement protocol to monitor and control the molecular occupancy...
Article
In this review, we focus on the early events in the process of fibroblast spreading on fibronectin matrices of different rigidities. We present a focused position piece that illustrates the many different tests that a cell makes of its environment before it establishes mature matrix adhesions. When a fibroblast is placed on fibronectin-coated glass...
Article
Full-text available
Although the shapes of organisms are encoded in their genome, the developmental processes that lead to the final form of vertebrates involve a constant feedback between dynamic mechanical forces, and cell growth and motility. Mechanobiology has emerged as a discipline dedicated to the study of the effects of mechanical forces and geometry on cell g...
Article
Full-text available
Cells test the rigidity of the extracellular matrix by applying forces to it through integrin adhesions. Recent measurements show that these forces are applied by local micrometre-scale contractions, but how contraction force is regulated by rigidity is unknown. Here we performed high temporal-and spatial-resolution tracking of contractile forces b...
Article
Full-text available
Treatment of cultured cells with inhibitors of actomyosin contractility induces rapid deterioration of stress fibers, and disassembly of the associated focal adhesions (FAs). In this study, we show that treatment with the Rho kinase inhibitor Y-27632, which blocks actomyosin contractility, induces disarray in the FA-associated actin bundles, follow...
Article
Integrin-mediated cell adhesions to the extracellular matrix (ECM) contribute to tissue morphogenesis and coherence and provide cells with vital environmental cues. These apparently static structures display remarkable plasticity and dynamic properties: they exist in multiple, interconvertible forms that are constantly remodeled in response to chan...
Article
The trafficking, membrane localization and lipid raft association of oncogenic Ras proteins dictate their isoform-specific biological responses. Accordingly, their spatiotemporal dynamics are tightly regulated. While extensively studied for H- and K-Ras, such information on N-Ras, an etiological oncogenic factor, is limited. Here, we report a novel...
Article
Non-integral membrane proteins frequently act as transduction hubs in vital signaling pathways initiated at the plasma membrane (PM). Their biological activity depends on dynamic interactions with the PM, which are governed by their lateral and cytoplasmic diffusion and membrane binding/unbinding kinetics. Accurate quantification of the multiple ki...
Article
Full-text available
Focal adhesions (FAs) have key roles in the interaction of cells with the extracellular matrix (ECM) and in adhesion-mediated signaling. These dynamic, multi-protein structures sense the ECM both chemically and physically, and respond to external and internal forces by changing their size and signaling activity. However, this mechanosensitivity is...
Article
Focal adhesions (FAs) are large clusters of transmembrane receptors of the integrin family and a multitude of associated cytoplasmic "plaque" proteins, which connect the extracellular matrix-bound receptors with the actin cytoskeleton. The formation of nearly stationary FAs defines a boundary between the dense and highly dynamic actin network in la...
Article
Full-text available
Focal adhesions (FAs) are specialized membrane-associated multi-protein complexes that link the cell to the extracellular matrix and play crucial roles in cell-matrix sensing. Considerable information is available on the complex molecular composition of these sites, yet the regulation of FA dynamics is largely unknown. Based on a combination of FRA...
Article
[This corrects the article on p. e4304 in vol. 4, PMID: 19172999.].
Data
2nd figure for the Supporting Information (0.60 MB EPS)
Data
1st figure for the Supporting Information (0.84 MB EPS)
Data
Full-text available
1st table for the Supporting Information (0.09 MB PDF)
Article
Mit der Natur gegen Amyloide: Insulin ist ein natürlicher Inhibitor der Amyloidbildung durch Amylin. Die wechselwirkenden Domänen der beiden Proteine wurden mithilfe eines vereinfachenden Ansatzes identifiziert (siehe Schema). Auf der Grundlage des molekularen Mechanismus der physiologischen Wechselwirkung könnten peptidmimetische Therapeutika für...

Questions

Questions (3)
Question
Hi, I am looking for data regarding changes in PDMS (sylgard 184) stiffness over time after curing. Is it safe to say that after curing the Young's modulus stays relatively stable over long periods of time (weeks, months)?
Thanks in advance.
Question
Hi, does anyone have experience with an Ossila spin coater? Any reviews/recommendations will be greatly appreciated.
Question
I found many reports of ATP concentration in muscle cells, but not in non-muscle cells. Specifically, I am interested in the ATP concentration (in uM) in fibroblasts.
Thank you.

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