The microenvironment dictates glycocalyx construction and immune surveillance

Kevin M Tharp; Sangwoo Park; Greg A Timblin; Alicia L Richards; Jordan A Berg; Nicholas M Twells; Nicholas M Riley; Egan L Peltan; D Judy Shon; Erica Stevenson; Kimberly Tsui; Francesco Palomba; Austin E Y T Lefebvre; Ross W Soens; Nadia M E Ayad; Johanna Ten Hoeve-Scott; Kevin Healy; Michelle Digman; Andrew Dillin; Carolyn R Bertozzi; Danielle L Swaney; Lara K Mahal; Jason R Cantor; Matthew J Paszek; Valerie M Weaver

doi:10.21203/rs.3.rs-3164966/v1

The microenvironment dictates glycocalyx construction and immune surveillance

Res Sq [Preprint]. 2023 Aug 16:rs.3.rs-3164966. doi: 10.21203/rs.3.rs-3164966/v1.

Authors

Kevin M Tharp¹, Sangwoo Park², Greg A Timblin¹, Alicia L Richards³, Jordan A Berg⁴, Nicholas M Twells⁵, Nicholas M Riley⁶, Egan L Peltan^{7

8}, D Judy Shon⁶, Erica Stevenson³, Kimberly Tsui⁹, Francesco Palomba¹⁰, Austin E Y T Lefebvre¹¹, Ross W Soens¹², Nadia M E Ayad¹, Johanna Ten Hoeve-Scott¹³, Kevin Healy¹⁴, Michelle Digman¹⁰, Andrew Dillin⁹, Carolyn R Bertozzi¹⁴, Danielle L Swaney³, Lara K Mahal⁵, Jason R Cantor¹⁵, Matthew J Paszek¹⁶, Valerie M Weaver^{1

17}

Affiliations

¹ Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
² Field of Biophysics, Cornell University, Ithaca, NY 14850, USA.
³ Quantitative Biosciences Institute (QBI) and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA.
⁴ Department of Biochemistry, University of Utah, Salt Lake City, UT 84112, USA.
⁵ Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
⁶ Department of Chemistry, Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
⁷ Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford CA USA 94305.
⁸ Sarafan ChEM-H, Stanford University, Stanford, CA USA 94305.
⁹ Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94597, USA.
¹⁰ Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, California, CA 92697, USA.
¹¹ Calico Life Sciences, South San Francisco, CA, USA.
¹² Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
¹³ UCLA Metabolomics Center, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
¹⁴ Department of Chemical and Systems Biology, Sarafan ChEM-H and Howard Hughes Medical Institute, Stanford University, Stanford, CA USA 94305.
¹⁵ Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry and Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
¹⁶ Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14850, USA.
¹⁷ Department of Bioengineering and Therapeutic Sciences, Department of Radiation Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA 94143, USA.

Abstract

Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium.

Keywords: ECM; Mechanopharmacology; bleb; glycoform; glycome; glycosylation; immune surveillance; lectin array; lectin microarray; mechano-metabolic; metabolism; microenvironment; sialic acid.

Publication types

Preprint

Abstract

Publication types

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