03/10/2016

A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force

Title: A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force
Authors:

Fouzia Bano, Suneale Banerji, Mark Howarth, David G. Jackson & Ralf P. Richter

Journal: Sci. Rep. 6, 34176; doi: 10.1038/srep34176 (2016)

The interactions of specialized extracellular sugars from the glycosaminoglycan (GAG) family with proteins are important for the correct communication of cells with their environment. It is now also well established that mechanical stimuli are important for cellular communication. In this study, Bano et al have devised a method to study how bonds between GAGs and proteins respond to directed mechanical forces. The method exploits purpose-designed surfaces that afford immobilization of GAGs and proteins at controlled nanoscale organizations. It enables the study of individual molecular bonds but also how several bonds act in concert, an aspect that is particularly important for GAGs because these are polymers and thus can bind several proteins simultaneously.
The authors applied the method to study the interaction of the GAG hyaluronan (HA) with CD44, a cell surface receptor that is important for the capture of cells by blood vessel walls and subsequent cell traffic into adjacent tissues. The molecular level insights gained should help understanding the regulation of the trafficking of immune cells (in inflammation), stem cells (in tissue repair) and cancer cells (in metastasis). This versatile platform technology should be widely applicable for elucidating molecular mechanisms underlying the response of extracellular matrix and cell surface receptors to mechanical forces.
Link to paper (open access): www.nature.com/articles/srep34176