# Regulation of cell function by mechanical properties of biopolymer networks and lipid bilayers

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2020 · $363,897

## Abstract

Project Summary
 Many aspects of cell biology as well as tissue physiology and the proper functioning of organisms are
essentially problems in material science. The structures and reactions that enable proper functioning of an
organism need to produce movements that are greater than those generated by random Brownian motion.
Cells need to build structures that are strong enough to resist gravitational forces as well as the mechanical
stresses that are generated by the same molecular structures and cellular assemblies that evolved to generate
movement and force. A related problem in soft matter is to understand the physical chemistry and dynamics of
the phospholipid bilayer that forms the cell membrane and orchestrates the signals generated at the cell
membrane and sent to the interior. This MIRA application combines two physical studies. One is focused on
the mechanical properties of purified biopolymer networks, intact cells, and whole tissues. The second
involves biophysical and biochemical characterizations of lipid bilayers containing anionic signaling lipids to
determine how these lipids distribute in the dynamic membrane and how this organization impacts their control
of intracellular protein targets.
 We have characterized and worked with theorists to explain the striking nonlinear elastic response of
semi-flexible polymeric networks, with emphasis on the cytoskeletal intermediate filament protein vimentin, and
shown how these physical models help explain cell and tissue mechanism. We have also shown how important
viscoelastic properties of the substrate are to cell phenotypes and have developed new materials by which to
study them. In membrane studies, we collaborate with molecular dynamics experts to produce a coherent
model of the structures and motions of anionic signaling lipids such as PIP2 ranging from the atomic to the
molecular, to the macroscopic membrane scale. Biochemical and cellular studies show that the spatial
distribution of these lipids in bilayers impacts the way they control cytoskeletal actin assembly at the
cytoplasm/membrane interface.
 Future work will build on these studies in three different areas. We will use our established models of
semiflexible networks to determine why vimentin networks, in contrast to those formed by stiffer polymers,
become stiffer when compressed, whereas crosslinked actin or microtubules become softer. We will also
extend our studies of extracellular polymers and cells to intracellular systems: cytoskeletal networks
containing membrane-bounded organelles, and crosslinked DNA or chromatin with the liquid particles and
organelles contained in the nuclear matrix. Here we will use our newly developed method to prepare intact
metabolically active nuclei surrounded by a thin layer or cytoplasm and a plasma membrane, and determine
how the perinuclear vimentin cage influences the structure and mechanical response of the nucleus.
Membrane studies will use our previous methods to alter PIP2 distrib...

## Key facts

- **NIH application ID:** 9930360
- **Project number:** 1R35GM136259-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Paul A Janmey
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,897
- **Award type:** 1
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930360

## Citation

> US National Institutes of Health, RePORTER application 9930360, Regulation of cell function by mechanical properties of biopolymer networks and lipid bilayers (1R35GM136259-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9930360. Licensed CC0.

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