# Biomechanical Regulation of Microbial Self-Organization in Confined Environments

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $325,815

## Abstract

Title: Biomechanical regulation of microbial self-organization in confined environments
Inside hosts, microbes grow under spatial constraints and frequently become so crowded that mechanical
stresses influence their behavior. For example, within humans, microbes often form fine-structured aggregates
in cavities on teeth, skin follicles, or crypt-like structures in the colon, which are increasingly recognized as an
important factor influencing human health. Although new layers of mechanical regulation of collective microbial
growth and motion have emerged in recent years, we know little about how such regulation influences the self-
organization of microbial communities. The main challenges are to experimentally monitor and theoretically
model the feedback between forces and growth at the same time and across multiple scales.
The objective of the proposed research is to quantify and model the direct and indirect feedback between growth
and mechanical forces in order to explain and predict the self-organization of dense cellular populations.
To this end, the P.I. proposes microfluidic and lineage tracking experiments spanning cellular to community-level
scales, as well as extrapolating simulations and theory. The proposed research leverages the intense dialog
between theory and experiment cultivated in his laboratory to achieve a predictive understanding of self-
organization in microbial populations in terms of the joint actions of individual cells.
The P.I. has two specific aims. First, he will identify and characterize physiological adaptations that enable
microbial populations to sustain large mechanical stresses and cell shape deformations. Understanding such
direct feedback between forces and growth will illuminate the role of forces in the pathogenic invasion of hosts,
which is a key step for virulence. Second, he will elucidate how dense microbial populations establish in tight
micro-environments, how they fend off invaders, turn over and adapt. Answering these questions will inform
strategies to promote or perturb a resilient microbial ecosystem in the gut or other crowded environments.
The proposed work develops state-of-the-art microfluidic techniques that enable automated spatio-temporal
tracking of cells and a novel strategy to track evolutionary processes, under defined mechanical boundary
conditions. The simulations developed synthesize modern population genetic theory with feature-rich biophysical
simulations and bridge the gap in spatio-temporal scales between laboratory experiments and natural
populations. The planned novel microfluidic devices and computer simulations will be of broad utility to the
biophysics community for the goal of dissecting collective properties of microbial populations.
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## Key facts

- **NIH application ID:** 10445778
- **Project number:** 2R01GM115851-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Oskar Hallatschek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $325,815
- **Award type:** 2
- **Project period:** 2015-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445778

## Citation

> US National Institutes of Health, RePORTER application 10445778, Biomechanical Regulation of Microbial Self-Organization in Confined Environments (2R01GM115851-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10445778. Licensed CC0.

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