# Mitosis in Confining Microenvironments

> **NIH NIH R01** · PURDUE UNIVERSITY · 2024 · $247,821

## Abstract

PROJECT SUMMARY
Cell division underlies the development of humans from embryos to full-grown adults, regenerative processes
such as wound healing, and diseases such as cancer. While much is known about the intracellular aspects of
mammalian cell division, less is known about the extracellular aspects of cell division. In many physiological
contexts, cells divide in mechanically confining microenvironments, including dense extracellular matrices
(ECMs) and growing tumors. Cell division requires extensive morphological changes, including significant growth
during the G1 phase of the cell cycle and elongation along the mitotic axis during mitosis, or mitotic elongation.
Both growth and mitotic elongation are strictly required for successful cell division. A mechanically confining
microenvironment provides a physical barrier to both cell growth and mitotic elongation, and cells must overcome
this confinement for successful cell division. Our recent studies have shown that single dividing cells in three-
dimensional (3D) matrices generate protrusive forces along the mitotic axis to drive mitotic elongation via a
combination of interpolar spindle elongation and cytokinetic ring contraction. We have also found that cell growth
during the G1 phase is mediated by outward force generation. However, it remains unclear how these forces
and their underlying mechanisms adapt to confining microenvironments with a wide range of stiffness and
viscoelasticity. In this project, we will determine how cells tune extracellular forces to sustain cell division in highly
confining microenvironments, using a powerful combination of rigorous agent-based modeling and experiments
with engineered biomaterials for 3D cell culture. We hypothesize that in microenvironments with increased
confinement, i) protrusive activity increases to make space and activate mechanosensitive channels for driving
G1 phase cell growth via increased osmotic pressure, and ii) enhanced cytokinetic ring contraction drives mitotic
elongation. The main hypothesis will be tested by pursuing the following three aims: (1) Determine how mitotic
elongation of isolated cells within highly confining microenvironments is accomplished via a novel force feedback
mechanism; (2) Define how isolated cells achieve G1 phase cell growth in highly confining microenvironments;
and (3) Establish how growth and mitotic elongation of cells in growing spheroids induce overall expansion of
spheroids in highly confining microenvironments. The proposed research project is significant because it will
reveal how cells modulate their force generation, to drive cell growth and mitotic elongation for cell division in
physiologically relevant microenvironments, and also elucidate the role of matrix remodeling and multicellular
cooperation in cell division. The approach is innovative because of i) the development and use of agent-based
models that can rigorously capture the most important aspects of cell growth, mitotic elongation, a...

## Key facts

- **NIH application ID:** 10934338
- **Project number:** 5R01GM151628-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Taeyoon Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $247,821
- **Award type:** 5
- **Project period:** 2023-09-25 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934338

## Citation

> US National Institutes of Health, RePORTER application 10934338, Mitosis in Confining Microenvironments (5R01GM151628-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10934338. Licensed CC0.

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