EPH/EPHRIN regulates cellular organization by actomyosin contractility effects on cell contacts

Abigail A Kindberg; Vasudha Srivastava; Jonathon M Muncie; Valerie M Weaver; Zev J Gartner; Jeffrey O Bush

doi:10.1083/jcb.202005216

EPH/EPHRIN regulates cellular organization by actomyosin contractility effects on cell contacts

J Cell Biol. 2021 Jun 7;220(6):e202005216. doi: 10.1083/jcb.202005216.

Authors

Abigail A Kindberg^{1

2

3

4

5}, Vasudha Srivastava⁶, Jonathon M Muncie^{7

8

9

10}, Valerie M Weaver^{4

7

8

11

12

13

14

9}, Zev J Gartner^{6

15

16}, Jeffrey O Bush^{1

2

3

4}

Affiliations

¹ Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA.
² Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA.
³ Institute for Human Genetics, University of California, San Francisco, San Francisco, CA.
⁴ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA.
⁵ Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA.
⁶ Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA.
⁷ Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, San Francisco, CA.
⁸ Department of Surgery, University of California, San Francisco, San Francisco, CA.
⁹ Helen Diller Family Cancer Research Center, University of California, San Francisco, San Francisco, CA.
¹⁰ Graduate Program in Bioengineering, University of California, San Francisco, and University of California, Berkeley, San Francisco, CA.
¹¹ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA.
¹² Department of Anatomy, University of California, San Francisco, San Francisco, CA.
¹³ Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
¹⁴ UCSF Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
¹⁵ Center for Cellular Construction, University of California, San Francisco, San Francisco, CA.
¹⁶ Chan Zuckerberg Biohub, San Francisco, CA.

Abstract

EPH/EPHRIN signaling is essential to many aspects of tissue self-organization and morphogenesis, but little is known about how EPH/EPHRIN signaling regulates cell mechanics during these processes. Here, we use a series of approaches to examine how EPH/EPHRIN signaling drives cellular self-organization. Contact angle measurements reveal that EPH/EPHRIN signaling decreases the stability of heterotypic cell:cell contacts through increased cortical actomyosin contractility. We find that EPH/EPHRIN-driven cell segregation depends on actomyosin contractility but occurs independently of directed cell migration and without changes in cell adhesion. Atomic force microscopy and live cell imaging of myosin localization support that EPH/EPHRIN signaling results in increased cortical tension. Interestingly, actomyosin contractility also nonautonomously drives increased EPHB2:EPHB2 homotypic contacts. Finally, we demonstrate that changes in tissue organization are driven by minimization of heterotypic contacts through actomyosin contractility in cell aggregates and by mouse genetics experiments. These data elucidate the biomechanical mechanisms driving EPH/EPHRIN-based cell segregation wherein differences in interfacial tension, regulated by actomyosin contractility, govern cellular self-organization.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Actin Cytoskeleton / physiology*
Actomyosin / physiology*
Animals
Cell Adhesion*
Cell Movement*
Ephrins / genetics
Ephrins / metabolism*
HEK293 Cells
Humans
Mice
Morphogenesis
Protein Binding
Receptors, Eph Family / genetics
Receptors, Eph Family / metabolism*
Signal Transduction

Substances

Ephrins
Actomyosin
Receptors, Eph Family

Abstract

Publication types

MeSH terms

Substances

Grants and funding