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Oncotically Driven Control over Glycocalyx Dimension for Cell Surface Engineering and Protein Binding in the
Erika M J Siren1,2, Rafi Chapanian1,3, Iren Constantinescu1,3
1Centre for Blood Research, Life Sciences Centre, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Scientific Reports
|May 17, 2018
Summary
This study introduces a novel method using macromolecular crowding to control cell surface reactions. This technique enhances binding to the outermost glycocalyx layer, improving cell therapies and understanding cell surface interactions.
Area of Science:
- Biochemistry
- Cell Biology
- Biomaterials Science
Background:
- The glycocalyx, a complex carbohydrate layer on cell surfaces, plays crucial roles in cell-cell interactions and immune responses.
- Controlling reactivity on the cell surface, particularly within the glycocalyx, is challenging due to its intricate structure.
- Understanding and manipulating glycocalyx structure is vital for applications in medicine and biotechnology.
Purpose of the Study:
- To develop a simple technique for redirecting cell surface reactions to the outermost region of the glycocalyx.
- To investigate the mechanism of reactivity control using macromolecular crowding.
- To demonstrate the biological significance of this technique in camouflaging cell surface antigens.
Main Methods:
- Utilized macromolecular crowding with inert polymers to alter glycocalyx proteoglycan accessibility.
- Applied cell-surface reactive probes to assess reactivity control in the 'z'-direction.
- Studied the effect of crowders on HUVEC glycocalyx structure and binding of various agents.
- Demonstrated camouflage of red blood cell surface antigens (RhD and CD47) using crowding-enhanced polymer grafting.
Main Results:
- Macromolecular crowding induced an oncotically driven collapse of the glycocalyx brush structure.
- This collapse redirected reactivity to the outermost glycocalyx surface, enhancing binding of polymers, protein markers, and antibodies.
- Crowding-assisted polymer grafting significantly decreased accessibility to Rhesus D (RhD) and CD47 proteins on red blood cells.
- The technique proved effective across multiple cell types.
Conclusions:
- Macromolecular crowding offers a versatile strategy for controlling cell surface reactivity and engineering the glycocalyx.
- This method provides new tools for probing glycocalyx structure and function.
- The technique holds promise for improving cell-based therapies by modulating cell surface antigen presentation.
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