Multi-lipid synergy in biolubrication: natural redundancy vs. natural selection

Phospholipid surface assemblies are crucial ingredients in reducing the boundary friction of articular cartilage in synovial joints such as hips and knees, of central importance to their homeostasis and to tissue-wear-related diseases such as osteoarthritis. From the point of view of biolubrication, the very large number of different lipids in joints begs the question of whether this is natural redundancy, or does this multiplicity confer any benefits, possibly through natural selection. Here we demonstrate that particular combinations of lipids present in joints may carry a clear benefit for their lubricating properties. Using progressively more complex mixtures of lipids representative of those in joints, and measuring their interactions using a uniquely-sensitive surface forces balance at physiologically-relevant salt concentrations and pressures, we show that different lipid combinations lead to very significant differences in their efficacy as boundary lubricants. This points to a clear synergy arising from the multiple lipid types in the lubricating layers, provides insight into the role of lipid type proliferation in synovial joints, of possibly evolutionary origins, and may suggest new treatment modalities for osteoarthritis. We identify parameters of lipid-based boundary layers that might contribute to improved boundary lubrication in the light of the present study. Finally, we describe a possible approach based on molecular dynamics (MD) to emulating such optimal lipid combinations, and provide proof-of-concept MD simulations to illustrate this approach.