About

Paul A. Janmey, Ph.D., is a Professor of Physiology at the University of Pennsylvania and a member of the Pennsylvania Muscle Institute. He also serves as the Associate Director of the Institute for Medicine and Engineering at UPenn. His research focuses on cell mechanics, cytoskeleton, phosphoinositide signaling, and cell mechanics. His lab studies various aspects of cell mechanics, including how substrate stiffness influences cell structure, function, and growth across different cell types such as endothelial cells, fibroblasts, neurons, and astrocytes. They produce hydrogels linked with cell adhesion proteins to examine mechanical cues, and utilize imaging, scattering, and rheologic methods to analyze cytoskeletal polymers. Additionally, his work explores how changes in cell membrane structure mediated by inositol phospholipids lead to signaling pathways that remodel the cytoskeleton.

Research topics

• Materials science
• Biology
• Composite material
• Cell biology
• Physics
• Genetics
• Biophysics
• Condensed matter physics
• Biochemistry
• Nanotechnology
• Immunology
• Biomedical engineering
• Neuroscience

Selected publications

• BPS2026 – Tissue-dependent mechanosensing by cells derived from human tumors

  Biophysical Journal · 2026-02-01

  article
  PublisherDOI

• Role of nuclear ATPases in nuclear mechanics and cell migration through confined spaces: Opposite effects of BRG1 and cohesin

  Biophysical Journal · 2026-02-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Author response for "How to train your sponge: imprinting material memories in marine sponge tissue"

  2026-02-26

  peer-review
  PublisherDOI

• BPS2026 – Role of nuclear motor proteins in nuclear mechanics and cell migration through confined spaces

  Biophysical Journal · 2026-02-01

  article1st authorCorresponding
  PublisherDOI

• Cholesterol-containing lipid crystals can directly stiffen the rat steatotic liver before fibrosis

  Proceedings of the National Academy of Sciences · 2026-01-07

  articleOpen access

  Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver steatosis with cardiometabolic risk factors like dyslipidemia. Patients may progress from steatosis alone to complications such as fibrosis, end-stage liver disease, and hepatocellular carcinoma. The cause of progression is unclear. We previously showed that liver stiffening can drive fibrosis. However, the mechanical contributions of hepatic lipid and especially cholesterol accumulation are not known. We used rat dietary models to investigate how lipid accumulation affects liver mechanics. Liver stiffness was measured using rheology and magnetic resonance elastography, and associations between stiffness and lipid droplets (LDs) or cholesterol-containing lipid crystals were measured by microindentation-visualization. Polarized light, confocal reflection, and cryo-electron microscopy were employed to assess crystal abundance and structure. LDs and crystals extracted from livers were embedded in fibrous tissue mimics to isolate mechanical effects away from inflammation or fibrosis. Methyl-β-cyclodextrin perfusion was performed to assess whether cholesterol depletion reduced crystal abundance and tissue stiffness. Increased hepatic cholesterol storage led to the formation of cholesterol-containing lipid crystals in the liver. Steatotic livers with crystals stiffened before fibrosis while steatotic livers without crystals did not stiffen or fibrose. Lipid crystals stiffened tissue mimics while LDs did not, suggesting that crystals directly cause stiffening. Cholesterol depletion reduced crystal abundance and reverted tissue stiffness to near controls without changing inflammation, suggesting key roles for cholesterol in tissue stiffening. Lipid crystals cause profibrogenic liver stiffening, connecting high dietary cholesterol to MASLD progression, and may be a target for new diagnostic tools and therapeutics for progressive MASLD.

  PublisherOA PDFDOI

• Mechanical strain modulates enzymatic remodeling of fibrin networks

  Polymer · 2025-07-28

  articleOpen accessSenior authorCorresponding

  Mechanical forces are increasingly recognized as key regulators of protein structure and enzymatic activity in biological materials. Here, we investigate how mechanical strain modulates the activity of factor XIIIa-mediated crosslinking and plasmin-mediated proteolysis of fibrous networks formed by the semiflexible biopolymer fibrin. Using shear rheology, turbidity measurements, confocal imaging, and gel electrophoresis, we show that fibrin fiber networks subjected to volume-conserving shear strain during polymerization undergo significant alignment and strain stiffening. These mechanical deformations enhance the exposure of binding sites within the fibrin network, leading to increased enzymatic reactivity. Specifically, the activity of the transglutaminase Factor XIIIa is elevated in strained gels, correlating with greater covalent bond formation between adjacent fibrin subunits. Likewise, plasmin-mediated proteolysis of fibrin proceeds more rapidly in strained gels, particularly in load-bearing fibers responsible for mechanical stiffness. Our findings reveal that fibrin is a mechanoresponsive substrate whose biochemical remodeling is strongly influenced by its mechanical environment. Fibrin gels formed under shear strain exhibit an architecture of aligned fibers compared to that of randomly oriented fibers formed without strain. Fiber alignment under mechanical deformation enhances enzymatic remodeling, leading to increased rates of factor XIIIa-mediated crosslinking and plasmin-mediated fibrinolysis. • Mechanical strain during fibrin polymerization aligns fibers and induces strain stiffening. • Shear strain enhances factor XIIIa-mediated crosslinking of fibrin gel. • Plasmin-mediated fibrinolysis is accelerated in strained fibrin gels, particularly in stretched, load-bearing fibers. • Fibrin behaves as a mechanoresponsive material, linking structural mechanics to enzymatic remodeling.

  PublisherDOI

• Tissue-dependent mechanosensing by cells derived from human tumors

  npj Biological Physics and Mechanics. · 2025-08-06 · 2 citations

  articleOpen access

  Alterations of the extracellular matrix (ECM), including both mechanical (such as stiffening of the ECM) and chemical (such as variation of adhesion proteins and deposition of hyaluronic acid (HA)) changes, in malignant tissues have been shown to mediate tumor progression. To survey how cells from different tissue types respond to various changes in ECM mechanics and composition, we measured physical characteristics (adherent area, shape, cell stiffness, and cell speed) of 25 cancer and 5 non-tumorigenic cell lines on 7 different substrate conditions. Our results indicate substantial heterogeneity in how cell mechanics changes within and across tissue types in response to mechanosensitive and chemosensitive changes in ECM. The analysis also underscores the role of HA in ECM with some cell lines showing changes in cell mechanics in response to presence of HA in soft substrate that are similar to those observed on stiff substrates. This pan-cancer investigation also highlights the importance of tissue-type and cell line specificity for inferences made based on comparison between physical properties of cancer and normal cells. Lastly, using unsupervised machine learning, we identify phenotypic classes that characterize the physical plasticity, i.e., the distribution of physical feature values attainable, of a particular cell type in response to different ECM-based conditions.

  PublisherOA PDFDOI

• Extracellular vimentin is a damage-associated molecular pattern protein serving as an agonist of TLR4 in human neutrophils

  Cell Communication and Signaling · 2025-02-05 · 11 citations

  articleOpen access

  BACKGROUND: Vimentin is a type III intermediate filament protein that plays an important role in cytoskeletal mechanics. It is now known that vimentin also has distinct functions outside the cell. Recent studies show the controlled release of vimentin into the extracellular environment, where it functions as a signaling molecule. Such observations are expanding our current knowledge of vimentin as a structural cellular component towards additional roles as an active participant in cell signaling. METHODS: Our study investigates the immunological roles of extracellular vimentin (eVim) and its citrullinated form (CitVim) as a damage-associated molecular pattern (DAMP) engaging the Toll-like receptor 4 (TLR4) of human neutrophils. We used in vitro assays to study neutrophil migration through endothelial cell monolayers and activation markers such as NADPH oxidase subunit 2 (NOX2/gp91phox). The comparison of eVim with CitVim and its effect on human neutrophils was extended to the induction of extracellular traps (NETs) and phagocytosis of pathogens. RESULTS: Both eVim and CitVim interact with and trigger TLR4, leading to increased neutrophil migration and adhesion. CitVim stimulated the enhanced migratory ability of neutrophils, activation of NF-κB, and induction of NET formation mainly mediated through reactive oxygen species (ROS)-dependent and TLR4-dependent pathways. In contrast, neutrophils exposed to non-citrullinated vimentin exhibited higher efficiency in favoring pathogen phagocytosis, such as Escherichia coli and Candida albicans, compared to CitVim. CONCLUSIONS: Our study identifies new functions of eVim in its native and modified forms as an extracellular matrix DAMP and highlights its importance in the modulation of immune system functions. The differential effects of eVim and CitVim on neutrophil functions highlight their potential as new molecular targets for therapeutic strategies aimed at regulation of neutrophil activity in different pathological conditions. This, in turn, opens new windows of therapeutic intervention in inflammatory and immunological diseases characterized by immune system dysfunction, in which eVim and CitVim play a key role.

  PublisherDOI

• Modeling tumor transport and growth with poroelastic biopolymer networks

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-25 · 1 citations

  preprintOpen access

  The mechanical properties of the extracellular matrix (ECM) regulate tumor growth and invasion in the tumor microenvironment. Models of biopolymer networks have been used to investigate the impact of elasticity and viscoelasticity of ECM on tumor behavior. Under tumor compression, these networks also show poroelastic behavior that is governed by the resistance to water flow through their pores. This work investigates the hypothesis that poroelastic properties regulate tumor growth. Here, alginate hydrogels with tunable ionic and hybrid ionic/covalent crosslinking are used as a model biopolymer system. Hydrogel stiffness, viscoelasticity, and stress relaxation behavior were characterized using stepwise axial compression. Among these properties, we find poroelastic fluid outflow dominates ECM stress relaxation, as the measured water flux was significantly affected under compression. Continuum mechanics-based modeling was developed to formulate and calculate the chemical potential gradients of water (solvent) in the hydrogels under compression. This framework was extended into an advection-diffusion framework to quantify growth factor (solute) distribution under varying strengths of stress and diffusion indexed by the relative strength of convective to diffusive transport, characterized by the Péclet number. An agent-based computational simulation showed that tumor growth was affected by Péclet number. Together, these results highlight the role of the poroelastic properties of ECM on water flux and transport in the tumor microenvironment.

  PublisherOA PDFDOI

• Silk Fibroin‐Based Matrices for the Guidance of Cell Interaction, Tissue Regeneration, and Crosstalk

  Macromolecular Bioscience · 2025-06-29 · 2 citations

  review

  The interactions between cells and the extracellular matrix are essential regulators of cell behaviors such as adhesion, proliferation, migration, differentiation, and function. From the perspective of tissue regeneration, some physicochemical characteristics of the material, including hydrophilicity, topology, and charge of the material surface, can significantly affect cell adhesion, proliferation, and differentiation. Many biomaterials are introduced for tissue engineering scaffolds, biomimicking natural tissues. Among the biomaterials, silk proteins (fibroin and sericin) have many excellent characteristics, making them ideal candidates for regenerative medicine. Several studies have tuned silk fibroin characteristics to specify cell adhesion, proliferation, and stem cell differentiation by combining fibroin with other materials, coating, modification, and biofunctionalization. In the current review article, the essential properties of silk fibroin-based scaffolds (presence of cell adhesion motifs, wettability, charge, elasticity) and their influences on cell adhesion, proliferation, and migration, as well as their biodegradation and the body's immune response are discussed. In addition, the crosstalk between silk fibroin and various cells is discussed, as well as different methods for blending or biofunctionalization of silk fibroin with the aim of engineering a silk-based scaffold with a specifically tuned response to biological systems and subsequently affecting the behavior of the cells.

  PublisherDOI

Recent grants

• NIH Grant R01GM083272

  NIH · $2.0M · 2013

• Spatial control of actin assembly by phosphoinositides

  NIH · $1.8M · 2015–2020

• NIH Grant R23AM035750

  NIH · $50k · 1988

• NIH Grant R29AR038910

  NIH · $262k · 1990

• NIH Grant R01DK083592

  NIH · $2.2M · 2018

Frequent coauthors

• Robert Bucki

  Medical University of Białystok

  118 shared

• Thomas P. Stossel

  84 shared

• Rebecca G. Wells

  University of Pennsylvania

  59 shared

• Katarzyna Pogoda

  58 shared

• Jay X. Tang

  Providence College

  57 shared

• Fitzroy J. Byfield

  55 shared

• Philip G. Allen

  52 shared

• Lisa A. Flanagan

  42 shared

Labs

• Paul A. Janmey LabPI