Evidence of “wired” drug-cell communication through micro-barrier well-array devices

Abstract

Treatments designed to intervene in conventional direct-drug-to-cell-binding communication have been hallmark approaches in designing new drug candidates. Given the random collision of molecules in living systems, this binding is laborious and too ineffective to precisely match the binding site. Therefore, it has been proposed that another non-chemical and non-electrical drug-cell communication channel, termed “bindingless” or “wired”, could exist to impact signal transduction. Here we present the use of a micro-barrier well-array device to explore the unidentified bindingless anti-cancer mechanism. The device involves a 95-μm polydimethylsiloxane barrier to compartmentalize cancer cells and chemotherapeutic drugs. The lack of permeation of solutions across the device barrier was validated. Paclitaxel diluted in medium significantly inhibited the growth of prostate PC-3 cancer cells over a 95-μm barrier instead of cisplatin. The inhibition was attenuated by diluting drugs in other solvents, such as deionized water and phosphate-buffered saline. In addition, the orientation of magnetic field could partially dominate the “wired” communication. The collective data provide the experimental evidence of the postulated “wired” drug-cell communication as a potent in anti-cancer mechanism. These findings may inform cell biology investigations and stimulate studies of new physical and chemical phenomena.