A high throughput screening system for studying the effects of applied mechanical forces on reprogramming factor expression

Abstract

Mechanical forces are important in the regulation of physiological homeostasis and the development of disease. The application of mechanical forces to cultured cells is often performed using specialized systems that lack the flexibility and throughput of other biological techniques. In this study, we developed a high throughput platform for applying complex dynamic mechanical forces to cultured cells. We validated the system for its ability to accurately apply parallel mechanical stretch in a 96 well plate format in 576 well simultaneously. Using this system, we screened for optimized conditions to stimulate increases in Oct-4 and other transcription factor expression in mouse fibroblasts. Using high throughput mechanobiological screening assays, we identified small molecules that can synergistically enhance the increase in reprograming-related gene expression in mouse fibroblasts when combined with mechanical loading. Taken together, our findings demonstrate a new powerful tool for investigating the mechanobiological mechanisms of disease and performing drug screening in the presence of applied mechanical load.

Document Details

Document Type
Pub Defense Publication
Publication Date
Sep 22, 2020
Source ID
10.1038/s41598-020-72158-5

Entities

People

  • Aaron B Baker
  • Eun Yoon
  • Jason S. Lee
  • Lara Samarneh
  • Miguel Armenta Ochoa
  • Mitchell Wong
  • Pablo Maceda

Organizations

  • American Heart Association
  • Congressionally Directed Medical Research Programs
  • National Institutes of Health

Tags

Fields of Study

  • Biology

Readers

  • Image Processing and Computer Vision.
  • Materials Science (Mechanical Engineering).
  • Oncology (Cancer Research).