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Deciphering and steering population-level response under spatial drug heterogeneity on microhabitat structures
Zhijian Hu1,2,3, Kevin Wood1,3,4
1Department of Biophysics, University of Michigan, Ann Arbor, USA.
Biorxiv : the Preprint Server for Biology
|March 3, 2025
Summary
Understanding bacterial and cancer cell population dynamics is key for drug efficacy. This study reveals that spatial growth variations and microhabitat structure, not just drug dosage, determine population decline, offering new treatment strategies.
Area of Science:
- Mathematical Biology
- Computational Biology
- Systems Biology
Background:
- Cellular populations (bacteria, cancer) exist in heterogeneous environments.
- Migration and growth dynamics complicate predicting drug responses, impacting colonization and metastasis.
- Predicting population-level drug responses remains a challenge.
Purpose of the Study:
- To disentangle the effects of growth and migration on population dynamics in heterogeneous environments.
- To identify key factors determining population decline under drug treatment.
- To provide insights into optimizing drug dosing strategies.
Main Methods:
- Developed a mathematical model to decouple spatial growth variation and microhabitat structure effects.
- Analyzed network structures and their relationship to population dynamics.
- Derived conditions for robust population decline.
Main Results:
- Population decline is determined by spatial growth variation and microhabitat structure (a dynamic centrality measure).
- Network structure significantly influences population response, independent of overall density.
- Increasing edge density promotes population clearance, showing an inverse centrality-connectivity relationship.
Conclusions:
- Microhabitat structure and growth dynamics are critical, not just drug concentration.
- Network properties can predict divergent clinical outcomes under identical drug dosages.
- Findings offer new methods for interpreting treatment dynamics and optimizing drug delivery.
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