Water-binding strength as regulator of extracellular-matrix mechanics enables detection of swelling-associated biophysical alterations using MRI

Abstract Altered hygroscopic properties of the extracellular matrix (ECM), such as related to exudation, are characteristic for various pathologies including inflammation in injury, inherent swelling, or proteoglycan (PG) dysregulation. Mechanical properties of the ECM are key characteristics of various cell niches, capable of defining cell phenotype and fate, or of storing pathological information. Dehydration is known to alter ECM mechanics, but the role of the binding of water to the ECM remains unclear. Our data illustrate that the proportion of loosely to strongly bound water is a distinctive ECM property that regulates its mechanics and they suggest a crucial role of PGs for elastic and viscous characteristics. Osmolality and loosely bound water determine dynamic ECM properties. This understanding may pave the ground to diagnose related pathological tissue alterations non-invasively using combined MR T1 and T2* mapping. Eventually, the strength of water binding may be utilized as controlled cell-niche property to guide cell behavior.