Hypothetical models of talin-independent integrin activation. (A) Translocation of integrins to lipid microdomains, distinct regions of the plasma membrane enriched in cholesterols and unsaturated lipids, can change the tilt angle of β3 TMD and disrupt the TMD interaction. (B) Stretch of lipid bilayer may change the properties of lipid bilayers, leading to the change in TMD tilt angle and disruption of the α-β TMD interaction. (C) When one of TMDs in the integrin molecule interacts with other TMDs, the α-β TMD interaction in the integrin can be disrupted. The disrupted α-β TMD interactions can then activate integrins.