Article does not explain the origin of free-solution protein interaction signals.

Bornhop et al. (1) had shown that interactions between protein molecules in solution can be detected bymeasuring the solution refractive index shifts using a technique referred to as backscattering interferometry (BSI). The origin of the BSI signal was unclear. In a recent article in PNAS, Bornhop et al. (2) claim to provide an explanation of its origin. Based on a large body of published literature, they argue that solvation and conformational changes during protein interactions could have a large effect on BSI signal. However, other than pointing out this possibly important fact, this article does not really provide an explanation of the BSI signal origin for the following reasons.