# Investigating the dynamics and mechanics of CLASP-mediated microtubule-actin interactions by combining in vitro reconstitution with studies in primary lung fibroblasts

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $30,260

## Abstract

PROJECT SUMMARY/ABSTRACT
 The ability of fibroblasts to produce force is essential for maintenance of the extracellular matrix, cell
motility, and wound repair. Overactivated fibroblasts are linked to cardiovascular and pulmonary fibrosis due to
an excess of connective tissue causing scarring. This in turn results in an inability for proper tissue expansion
and can lead to myocardial infarction and difficulty in breathing. Force production by fibroblasts, in part, is driven
by interactions between microtubule and actin cytoskeletons, coordinated by crosslinking proteins to ensure
proper cell migration. Members of the CLASP (Cytoplasmic Linker Associated Protein) family of proteins have
been implicated in the cytoskeletal crosstalk in the context of fibroblast function. However, the specific dynamic
and mechanical interactions between microtubules and actin mediated by CLASPs remain elusive. This study
will use in vitro reconstitution of microtubules and actin with purified proteins and investigations in human lung
fibroblasts to elucidate interactions between microtubules and actin mediated by CLASP2. Preliminary results
demonstrate that CLASP2⍺ directly interacts with actin in vitro, with a stronger colocalization with bundled actin
filaments, and facilitates interactions between microtubules and actin. First, the preferential actin substrate for
CLASP2-mediated crosslinking of actin with microtubules will be characterized. Then, the individual and global
CLASP2-mediated interactions with dynamic microtubules and actin will be quantified in vitro and in human lung
fibroblasts. Second, the mechanical properties of CLASP2-crosslinked microtubule-actin polymers will be
characterized by using microfluidic flow to investigate the strength and mechanical stability in vitro. Furthermore,
atomic force microscopy will be used to measure the elastic properties of human lung fibroblast cells. The
combination of in vitro reconstitution and experiments in human lung fibroblasts will elucidate the biochemical
and mechanical mechanisms underlying microtubule-actin coordination by CLASP2. This fellowship award will
not only fund the proposed project to elucidate the dynamics and mechanics of microtubule and actin interactions
in the context of human fibroblasts but will also support the applicant’s training in interdisciplinary science. The
project involves a collaboration between two laboratories with complementary expertise in biochemical
reconstitution and cell biology. The applicant will apply her background in the physical sciences, along with
dedicated support from the sponsor, co-sponsor, and thesis committee, composed of faculty in Cell and
Developmental Biology, Biochemistry, Physics, and Biomedical Engineering, to complete the proposed project.
Elucidating the mechanisms underlying fibroblast force production by using multidisciplinary approaches will
provide an important understanding of processes that drive cardio and pulmonary fibrosis.

## Key facts

- **NIH application ID:** 10065901
- **Project number:** 1F31HL151033-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Nicole Christina Rodgers
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,260
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065901

## Citation

> US National Institutes of Health, RePORTER application 10065901, Investigating the dynamics and mechanics of CLASP-mediated microtubule-actin interactions by combining in vitro reconstitution with studies in primary lung fibroblasts (1F31HL151033-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065901. Licensed CC0.

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