Viola Vogel

• PhD
• Professor (Full) at ETH Zurich

Tendon ruptures and tendinopathies represent a major part of musculoskeletal injuries. Due to the hypovascular and hypocellular nature of tendons, the natural healing capacity is slow and limited. Cell-free approaches for tendon injuries are being investigated as the next generation of therapeutic treatments. The aim of this study was to compare th...

The continuously remodeled extracellular matrix (ECM) plays a pivotal role in gastrointestinal health and disease, yet its precise functions remain elusive. In this study, we employed laser capture microdissection combined with low-input proteomics to investigate ECM remodeling during Salmonella -driven inflammation. To complement this, we probed h...

Objectives: Increasing exercise intensity and performance output with superimposed vibration gains interest, especially in high-performance training. However, the additional benefit of vibration in passive stretching exercises and its mechanisms remain unclarified. Methods: Passive stretching with (ST+V) and without (ST) vibration (20 Hz) was perfo...

Objective: Due to its high relevance in sports and rehabilitation, the exploration of interventions to further optimize flexibility becomes paramount. While stretching might be the most common way to enhance range of motion (ROM), these increases could be optimized by imposing an additional activation of the muscle, such as mechanical vibratory sti...

Introduction: Hemophilia A (HA) is a rare genetic bleeding disorder caused by a deficiency of functional coagulation factor VIII (FVIII). Platelets have important functions throughout the various stages of hemostasis. Upon injury, platelets become activated in a pro-aggregatory state, and a subpopulation subsequently undergoes a phenotype shift to...

Izumo1:Juno-mediated adhesion between sperm and egg cells is essential for mammalian sexual reproduction. However, conventional biophysical and structural approaches have provided only limited functional insights. Using atomic force microscopy-based single-molecule force spectroscopy and all-atom steered molecular dynamic simulations, we explored t...

Glioblastoma is one of the most deadly human cancers characterized by high degrees of vascularization, but targeting its vasculature has resulted in very limited success so far. Angiogenesis, the growth of new blood vessels, is highly dynamic during brain development, enters a mostly quiescent state in the adult homeostatic brain, and is reactivate...

As one major problem after tendon rupture repair, surgeons are confronted with fibrotic adhesion formation of the healing tendon to the surrounding tissue. Although early active motion is recommended during rehabilitation, adhesions may lead to joint stiffness and a restricted range of motion. One viable option to counteract adhesion formation is t...

The continuously remodeled extracellular matrix (ECM) plays a pivotal role in gastrointestinal health and disease, yet its precise functions remain elusive. In this study, we employed laser capture microdissection combined with low-input proteomics to investigate ECM remodeling during Salmonella -driven inflammation. We also probed the mechanosensi...

Intestinal edema is a common manifestation of numerous gastrointestinal diseases and is characterized by the accumulation of fluid in the interstitial space of the intestinal wall. Technical advances in laser capture microdissection and low‐biomass proteomics now allow us to specifically characterize the intestinal edema proteome. Using advanced pr...

Background Endometriosis is characterized by the ectopic occurrence of endometrial tissue. Though considered benign, endometriotic lesions possess tumor-like properties such as tissue invasion and remodeling of the extracellular matrix. One major clinical hurdle concerning endometriosis is its diagnosis. The diagnostic modalities ultrasound and MRI...

Bone fracture healing is regulated by mechanobiological cues. Both, extracellular matrix (ECM) deposition and microvascular assembly determine the dynamics of the regenerative processes. Mechanical instability as by inter‐fragmentary shear or compression is known to influence early ECM formation and wound healing. However, it remains unclear how th...

Background Active and passive biomechanical properties of platelets contribute substantially to thrombus formation. Actomyosin contractility drives clot contraction required for stabilizing the hemostatic plug. Impaired contractility results in bleeding but is difficult to detect using platelet function tests. Objectives To determine how diminishe...

Dysfunctional extracellular matrices (ECM) contribute to aging and disease. Repairing dysfunctional ECM could potentially prevent age-related pathologies. Interventions promoting longevity also impact ECM gene expression. However, the role of ECM composition changes in healthy aging remains unclear. Here we perform proteomics and in-vivo monitoring...

Background: Platelets play an important role throughout the various stages of hemostasis. After vascular injury, platelets become activated in a pro-aggregatory state, and subsequently a subpopulation undergoes a phenotype shift to a pro-coagulant state. Pro-coagulant platelets bind to factor VIII (FVIII) and ensure efficient localization of FVIII...

Background: CAR-T cell therapy has transformed blood cancer treatment with promising clinical trial outcomes. However, access to this therapy has been limited due lengthy and complex CAR-T cell production process, resulting in a very costly therapy. To enhance patient welfare, establishment of innovative point-of-care solutions with a simplified an...

JUNO-IZUMO1 binding is the first known physical link created between the sperm and egg membranes in fertilization, however, how this initiates sperm-egg fusion remains elusive. As advanced structural insights will help to combat the infertility crisis, or advance fertility control, we employed all-atom Molecular Dynamics (MD) to derive dynamic stru...

Tissue transglutaminase 2 (TG2) plays a vital role in stabilizing extracellular matrix (ECM) proteins through enzymatic crosslinking during tissue growth, repair, and inflammation. TG2 also binds non-covalently to fibronectin (FN), an essential component of the ECM, facilitating cell adhesion, migration, proliferation, and survival. However, the in...

Carious lesions are bacteria-caused destructions of the mineralised dental tissues, marked by the simultaneous activation of immune responses and regenerative events within the soft dental pulp tissue. While major molecular players in tooth decay have been uncovered during the past years, a detailed map of the molecular and cellular landscape of th...

Intestinal edema is a common manifestation of numerous gastrointestinal diseases and is characterized by the accumulation of fluid in the interstitial space of the intestinal wall. Technical advances in laser capture microdissection and low-biomass proteomics now allow us to specifically characterize the intestinal edema proteome. Our data identifi...

Altered hygroscopic properties of the extracellular matrix (ECM), such as related to exudation, are characteristic for various pathologies including inflammation in injury, inherent swelling, or proteoglycan (PG) dysregulation. Mechanical properties of the ECM are key characteristics of various cell niches, capable of defining cell phenotype and fa...

Improper healing of the cornea after injury, infections or surgery can lead to corneal scar formation, which is associated with the transition of resident corneal keratocytes into activated fibroblasts and myofibroblasts (K–F/M). Myofibroblasts can create an extracellular matrix (ECM) niche in which fibrosis is promoted and perpetuated, resulting i...

Controlled tissue growth is essential for multicellular life and requires tight spatiotemporal control over cell proliferation and differentiation until reaching homeostasis. As cells synthesize and remodel extracellular matrix, tissue growth processes can only be understood if the reciprocal feedback between cells and their environment is revealed...

Glioblastoma is amongst the deadliest human cancers and is highly vascularized. Angiogenesis is very dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies including brain tumors. The onco-fetal axis describes the reactivation of fetal programs in tumors, but its relevance in endo...

The carious lesion is a bacteria caused destruction of tooth mineralized matrices marked by concurrent tissue reparative and immune responses in the dental pulp. While major molecular players in tooth pulp decay have been uncovered, a detailed map of the molecular and cellular landscape of the diseased pulp is still missing. Here we used single-cel...

Tracks rich in matrix and cells, as described in several cancer types, have immunosuppressive functions and separate tumor nests and stroma, yet their origin is unknown. Immunostainings of cryosections from mouse breast tumors show that these tracks are bordered by an endothelial-like basement membrane, filled with fibers of collagen adjacent to te...

Mutations and defects in nuclear lamins can cause major pathologies, including inflammation and inflammatory diseases. Yet, the underlying molecular mechanisms are not known. We now report that pro-inflammatory activation of macrophages, as induced by LPS or pathogenic E. coli, reduces Lamin-A/C levels to augment pro-inflammatory gene expression an...

Many inflammatory diseases that are responsible for a majority of deaths are still uncurable, in part as the underpinning pathomechanisms and how to combat them is still poorly understood. Tissue-resident macrophages play pivotal roles in the maintenance of tissue homeostasis, but if they gradually convert to proinflammatory phenotypes, or if blood...

Background Previously, we have exploited bacterial adhesins-derived fibronectin-binding peptides (FnBPs) for targeting mechanically altered fibronectin (Fn) fibrils within the cancer-associated extra-cellular matrix (ECM). However, despite the ability of FnBP probes to visualize pathological lesions, when labeled with metallic radionuclides and adm...

Although it is postulated that dysfunctional extracellular matrices (ECM) drive aging and disease, how ECM integrity assures longevity is unknown. Here, using proteomics and in-vivo monitoring of fluorescently tagged ECM proteins, we systematically examined the ECM composition during Caenorhabditis elegans aging revealing three distinct collagen dy...

Intimal hyperplasia (IH) represents a major challenge following cardiovascular interventions. While mechanisms are poorly understood, the inefficient preventive methods incentivize the search for novel therapies. A vessel‐on‐a‐dish platform is presented, consisting of direct‐contact cocultures with human primary endothelial cells (ECs) and smooth m...

Spermatogonial stem cells (SSCs) originate from gonocytes that differentiate from primordial germ cells (PGCs). In the developing mouse testis, expression of the gene LIM homeobox 1 (Lhx1) marks the most undifferentiated SSCs, which has not yet been reported for spermatogonia-like cells generated in vitro. Previously, it was shown that a chemical i...

Platelets interact with multiple adhesion proteins during thrombogenesis, yet little is known about their ability to assemble fibronectin matrix. In vitro three-dimensional superresolution microscopy complemented by biophysical and biochemical methods revealed fundamental insights into how platelet contractility drives fibronectin fibrillogenesis....

Mutations and defects in nuclear lamins can cause major pathologies in affected tissues. Recent studies have also established potential links between lamins, inflammation, and inflammatory diseases but the underlying molecular mechanisms are unknown. We now report that pro-inflammatory activation of macrophages reduces levels of Lamin-A/C to augmen...

Shear stress is extremely important for endothelial cell (EC) function. The popularity of 6-well plates on orbital shakers to impose shear stress on ECs has increased among biologists due to their low cost and simplicity. One characteristic of such a platform is the heterogeneous flow profile within a well. While cells in the periphery are exposed...

Shear stress is extremely important for endothelial cell (EC) function. The popularity of 6-well plates on orbital shakers to impose shear stress on ECs has increased among biologists due to their low cost and simplicity. One characteristic of such a platform is the heterogeneous flow profile within a well. While cells in the periphery are exposed...

During the development of the male germline, spermatogonial stem cells (SSCs) originate from gonocytes that differentiate from primordial germ cells (PGCs). In the developing and regenerating mouse testis, expression of the gene LIM homeobox 1 ( Lhx1 ) marks the most undifferentiated SSCs. However, an enrichment of Lhx1 expression in spermatogonia-...

Significance Microvilli are used by immune cells to sense the surface features of pathogens and antigen presenting cells. However, microvilli’s contribution in T cell signaling and activation is largely unknown. Here, we introduce a material-based platform for induction of microvilli formation in T cells, in which the dimensions of the microvilli c...

Vinculin plays a key role during the first phase of focal adhesion formation and interacts with the plasma membrane through specific binding of its Tail domain to the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Our understanding of the PIP2-Vinculin interaction has been hampered by contradictory biochemical and structural data. Here, we use...

The precise spatial localization of proteins in situ by super-resolution microscopy (SRM) demands their targeted labeling. Positioning reporter molecules as close as possible to the target remains a challenge in primary cells or tissues from patients that cannot be easily genetically modified. Indirect immunolabeling introduces relatively large lin...

T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanisms by which microvilli contribute to cell signaling and activation is...

Atherosclerosis is an arterial disease characterized by intravascular plaques. Disease hallmarks are vessel stenosis and hyperplasia, eventually escalating into plaque rupture and acute clinical presentations. Innate immune cells and local variations in hemodynamics are core players in the pathology, but their mutual relationship has never been inv...

Glioblastoma (GBM) is amongst the deadliest human cancers and is characterized by high levels of vascularisation. Angiogenesis is highly dynamic during brain development and almost quiescent in the adult brain, but is reactivated in vascular-dependent CNS pathologies such as brain tumors. Nucleolin (NCL) is a known regulator of cell proliferation a...

As part of our continuous efforts to develop a suitable fluorine-18 labeled positron emission tomography (PET) radioligand with improved imaging characteristics for imaging the GluN2B-bearing N-Methyl-D-aspartate receptors (NMDARs), we investigated in the current work ortho- and meta-fluorinated analogues of 18F-PF-NB1, a 3-benzazepine-based radiof...

The extracellular matrix (ECM) acts as reservoir for a plethora of growth factors and cytokines some of which are hypothesized to be regulated by ECM fiber tension. Yet, ECM fiber tension has never been mapped in healthy versus diseased organs. Using our recently developed tension probe derived from the bacterial adhesin FnBPA5, which preferentiall...

In article number 2000173, Vahid Hosseini, Viola Vogel, and co‐workers present a pulsatile flow system to mimic disease‐like extracellular matrix of vascular wall tissues and to gain insights into changes upon exposure to drugs taken to treat atherosclerosis or aneurysm. The cover image is an actual multistack of temporary color‐coded photos of flo...

Alterations of blood flow patterns strongly correlate with arterial wall diseases such as atherosclerosis and aneurysm. Here, a simple, pumpless, close‐loop, easy‐to‐replicate, and miniaturized flow device is introduced to concurrently expose 3D engineered vascular smooth muscle tissues to high‐velocity pulsatile flow versus low‐velocity disturbed...

Upon vascular injury, platelets are crucial for thrombus formation and contraction, but do they directly initiate early tissue repair processes? Using 3D super-resolution microscopy, micropost traction force microscopy, and specific integrin or myosin IIa inhibitors, we discovered here that platelets form fibrillar adhesions. They assemble fibronec...

Social distancing, washing hands and good hygiene are essential and currently the most potent methods available to curb down the unprecedented speed by which the new coronavirus is spreading across the globe. Even under lockdown, which is necessary to significantly reduce the number of people that get infected by an ill person, are there additional...

Vinculin is a universal adaptor protein that transiently reinforces the mechanical stability of adhesion complexes. It stabilizes mechanical connections that cells establish between the actomyosin cytoskeleton and the extracellular matrix via integrins or to neighboring cells via cadherins, yet little is known regarding its mechanical design. Vincu...

Cell-based tendon therapies with tenocytes as a cell source need effective tenocyte in vitro expansion before application for tendinopathies and tendon injuries. Supplementation of tenocyte culture with biomolecules that can boost proliferation and matrix synthesis is one viable option for supporting cell expansion. In this in vitro study, the impa...

A major problem after tendon laceration is the low mechanical strength of the repaired tissue. One viable strategy for improving the functional and biomechanical properties of ruptured and repaired tendons is the delivery of growth factors at the injury site. Here, bioactive and reversibly expandable double-layered emulsion and coaxially electrospu...

Abstract As we are approaching 20 years after the US National Nanotechnology Initiative has been announced, whereby most of that funding was spend to engineer, characterize and bring nanoparticles and nanosensors to the market, it is timely to assess the progress made. Beyond revolutionizing nonmedical applications, including construction materials...

To effectively translate bioactive scaffolds into a preclinical setting, proper sterilization techniques and storage conditions need to be carefully considered, as the chosen sterilization technique and storage condition might affect the structural and mechanical properties of the scaffolds, as well as the bioactivity and release kinetics of the in...

In a proof-of-concept study, a mechano-chromic hydrogel was synthesized here, via chemoenzymatic click conjugation of fluorophore-labeled fibronectin into a synthetic hydrogel co-polymers (i.e., poly-N-isopropylacrylamide / polyethelene glycol). The optical FRET...

Macromolecular crowding is used by tissue engineers to accelerate matrix assembly in vitro, however, most mechanistic studies focus on the impact of crowding on collagen fiber assembly and largely ignore the highly abundant provisional matrix protein fibronectin. We show that the accelerated collagen I assembly as induced by the neutral crowding mo...

A large number of extracellular matrix proteins have been found in phosphorylated states, yet little is known about how the phosphorylation of extracellular matrix proteins might affect cell functions. We thus tested the hypothesis whether the phosphorylation of fibronectin, a major adhesion protein, affects cell behavior. Controlled in vitro phosp...

DNA methylation patterns create distinct gene expression profiles. These patterns are maintained after cell division, thus enabling the differentiation and maintenance of multiple cell types from the same genome sequence. The advantage of this mechanism for transcriptional control is that chemical-encoding allows to rapidly establish new epigenetic...

In addition to their early-recognized functions in host defense and the clearance of apoptotic cell debris, macrophages play vital roles in tissue development, homeostasis, and repair. If misregulated, they steer the progression of many inflammatory diseases. Much progress has been made in understanding the mechanisms underlying macrophage signalin...

Tissue transglutaminase (TG2) is upregulated in the pathogenesis of a wide variety of chronic diseases. In this review special emphasis will be placed on fundamental mechanisms underlying the critical role of TG2 in fibroproliferative disorders. TG2 is best known for its cross-linking capacities in the extracellular space but has many critical and...

Recent progress in microengineering has included the demonstration of various micropumps; however, these pumps are typically driven by an external energy source such as an electrical power source. Thus, there is a limitation to the integration of such pumps into microdevices. Here, we report fabrication of the world smallest autonomous hybrid pump...

DNA methylation patterns create distinct gene expression profiles. These patterns are maintained after cell division, thus enabling the differentiation and maintenance of multiple cell types from the same genome sequence. The advantage of this mechanism for transcriptional control is that chemical-encoding allows to rapidly establish new epigenetic...

Macrophages respond to chemical/metabolic and physical stimuli, but their effects cannot be readily decoupled in vivo during pro-inflammatory activation. Here, we show that preventing macrophage spreading by spatial confinement, as imposed by micropatterning, microporous substrates or cell crowding, suppresses late lipopolysaccharide (LPS)-activate...

Myofibroblasts play central roles in orchestrating wound healing processes and, if remaining activated, drive disease progression such as fibrosis and cancer. Mechanical tension in the microenvironment is one major factor controlling the fibroblast-to-myofibroblast transition (FMT), and if misregulated, causes fibrosis and leads to approximately 45...

Haemostatic platelet function is intimately linked to cellular mechanics and cytoskeletal morphology. How cytoskeletal reorganizations give rise to a highly contractile phenotype that is necessary for clot contraction remains poorly understood. To elucidate this process in vitro, we developed a morphometric screen to quantify the spatial organizati...

A robust nanopillar platform with increased spatial resolution reveals that perinuclear forces, originating from stress fibres spanning the nucleus of fibroblasts, are significantly higher on these nanostructured substrates than the forces acting on peripheral adhesions. Many perinuclear adhesions embrace several nanopillars at once, pulling them i...

Haemostatic platelet function is intimately linked to cellular mechanics and cytoskeletal morphology. How cytoskeletal reorganizations give rise to a highly contractile phenotype that is necessary for clot contraction remains poorly understood. To elucidate this process in vitro , we developed a morphometric screen to quantify the spatial organizat...

Cells need to be anchored to extracellular matrix (ECM) to survive, yet the role of ECM in guiding developmental processes, tissue homeostasis, and aging has long been underestimated. How ECM orchestrates the deterioration of healthy to pathological tissues, including fibrosis and cancer, also remains poorly understood. Inquiring how alterations in...

Most systemic viral gene therapies have been limited by sequestration and degradation of virions, innate and adaptive immunity, and silencing of therapeutic genes within the target cells. Here we engineer a high-affinity protein coat, shielding the most commonly used vector in clinical gene therapy, human adenovirus type 5. Using electron microscop...

In article number 1702650, Vahid Hosseini, Viola Vogel, and co-workers present an innovative and cheap method to align 3D fibrillar scaffolds for surgical and tissue-engineering applications. This easy to scale-up method enables the creation of an aligned and highly porous 3D network of fibers with interconnected pores that are suitable for cell in...

Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor–β (TGF-β) a...

In native tissues, cellular organization is predominantly anisotropic. Yet, it remains a challenge to engineer anisotropic scaffolds that promote anisotropic cellular organization at macroscopic length scales. To overcome this challenge, an innovative, cheap and easy method to align clinically approved non-woven surgical microfibrillar scaffolds is...

Transformations of extracellular matrix (ECM) accompany pathological tissue changes, yet how cell-ECM crosstalk drives these processes remains unknown as adequate tools to probe forces or mechanical strains in tissues are lacking. Here, we introduce a new nanoprobe to assess the mechanical strain of fibronectin (Fn) fibers in tissue, based on the b...