Experimental work of reference \cite{Mangione_2013}

Focus is on D76N, the most amyloidogenic variant of b2m that is able to form readily amyloid fibrils in vitro under physiological extracellular conditions.
For this variant, the most common configuration of the His31-Pro32 bond is the non-native trans.
When interacting with a hydrophobic/hydrophilic interface, the protein is perturbed by several interactions: the most relevant is the hydrophobic force. One of the triggering factor is the  exposition of hydrophobic domains.
The model to describe the hydrophobic interaction energy between two apolar surfaces is :
\(E_{hydro}=-2\gamma\left(a-a_0\right)\exp\left(-\frac{d}{D_{hydro}}\right)\)
and then the hydrophobic force acting on the molecule is calculated as:\(F_{hydro}=-\left(\frac{dE_{hydro}}{dd}\right)=\frac{\left(-2\gamma\left(a-a_0\right)\exp\left(-\frac{d}{D_{hydro}}\right)\right)}{D_{hydro}}\)
considering the interfacial tension \(\gamma=\frac{50mJ}{m^2}\), the exposed area \(a_0=50\ A^2\), the hydrophobic decay length \(D_{hydro}=10\ A\), and \(a\left(d\right)=\left(a_0\left(1-\exp\left(-\frac{d}{D_{hydro}}\right)\right)^{-\frac{1}{2}}\right)\) it is possible to find, for a distance between 1 and 10 A, that the energies vary \(E_{hydro}=14.7-0.7\ \frac{kcal}{mol}\) and the forces between \(F_{hydro}=4.8-102\ pN\).
These intensities are strong enough to perturb the threedim structure of the b2m protein.
Contrarily to the wild type, D76N rapidly aggregates when agitated at 37.0°C, pH7.4 and in the presence of air/water interface (known to behave as a hydrophobic interface).