Chemical control over membrane-initiated steroid signaling with a DNA nanocapsule

Membrane-initiated steroid signaling (MISS) is a recently discovered aspect of steroidal control over cell function that has proved highly challenging to study due to its rapidity and ultrasensitivity to the steroid trigger [Chow RWY, Handelsman DJ, Ng MKC (2010) Endocrinology 151:2411-2422]. Fundamental aspects underlying MISS, such as receptor binding, kinetics of ion-channel opening, and production of downstream effector molecules remain obscure because a pristine molecular technology that could trigger the release of signaling steroids was not available. We have recently described a prototype DNA nanocapsule which can be programmed to release small molecules upon photoirradiation [Veetil AT, et al. (2017) Nat Nanotechnol 12:1183-1189]. Here we show that this DNA-based molecular technology can now be programmed to chemically trigger MISS, significantly expanding its applicability to systems that are refractory to photoirradiation.