# The mechanical role of the glycocalyx in cancer cell adhesion

> **NIH NIH K00** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $93,600

## Abstract

Project Summary
 Many types of cancer – such as recurrent glioblastoma multiform, which is invariably lethal – overexpress
bulky glycoproteins to form a thick glycocalyx layer. The glycocalyx physically separates the cell from its
surroundings, but recent work has shown that the glycocalyx can paradoxically increase adhesion to soft tissues
and therefore promote the metastasis of cancer cells. This surprising phenomenon occurs because the
glycocalyx forces adhesion molecules (called integrins) on the cell's surface into clusters. These integrin clusters
have cooperative effects that allow them to form stronger adhesions to surrounding tissues than would be
possible with equivalent numbers of un-clustered integrins. These cooperative mechanisms have been intensely
scrutinized in recent years; a more nuanced understanding of the biophysical underpinnings of glycocalyx-
mediated adhesion could uncover therapeutic targets, deepen our general understanding of cancer metastasis,
and elucidate general biophysical processes that extend far beyond the realm of cancer research.
 Here I present the hypothesis that the glycocalyx has the additional effect of increasing mechanical tension
experienced by clustered integrins. Integrins function as mechanosensors that undergo structure-switching into
“active” conformations when subjected to mechanical tension. As such, my hypothesis would, if true, suggest a
more immediate regulatory role of the glycocalyx in adhesion than previously realized. This hypothesis (which I
call the local organization hypothesis) is well-supported through indirect observation in the research literature
but has not been directly tested due to challenges associated with measuring mechanical tension on individual
biomolecules in live cells. However, I have devoted much of my career to developing DNA-based
mechanosensor tools that can be used to directly measure piconewton-scale integrin tension in live cells. Here
I propose to utilize these tools to test the local organization hypothesis and bring clarity to this rapidly-growing
research field. I plan to image integrin forces during the early stages of cellular adhesion and test for a set of
specific observations that would support or refute the local organization hypothesis. In parallel, I plan to leverage
my computational skills to test this hypothesis using a sophisticated chemomechanical simulation method.
 For my postdoctoral (K00) work, I will transition into translational work and develop tools that leverage the
principles of glycocalyx-mediated adhesion for cancer diagnostic purposes. Because glycocalyx-presenting
cancer cells adhere more readily to soft substrates, I will develop a flow-based method for detecting circulating
tumor cells (CTCs) using soft substrates and substrates of varying stiffness that facilitate mechanoselection of
glycocalyx-presenting cancer cells. This mechanoselection-based method will enable mechanical profiling of
CTCs to determine what types of tissue...

## Key facts

- **NIH application ID:** 10247898
- **Project number:** 4K00CA245789-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Aaron Blanchard
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $93,600
- **Award type:** 4N
- **Project period:** 2020-09-16 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247898

## Citation

> US National Institutes of Health, RePORTER application 10247898, The mechanical role of the glycocalyx in cancer cell adhesion (4K00CA245789-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247898. Licensed CC0.

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