free floating spike in vitro cultured human cells developed pathological state.<p>when a spike protien is expressed as an insertion into the cytoplasmic membrane there is very limited mobility, and less potential to approach ACE2 with appropriate orientation and energy for receptor ligand-interaction to occur, this would result in somewhat less interaction of the spike with the rennin angiotensin system[RAS]. a concern would be the possible development of abberant or deletion type spike protiens translated from undesirerable spike-mRNA species, the scenario of most concern would be a spike protien with malformed or deleted transmembrane domains, thus allowing a speudo spike protien to move freely outside the host cell.<p>this doesnt indicate that there is an unconceived problem, this publication is recognizing that perturbations of the RAS are highly consequential; a major part of covid pathology; and a hidden gotcha, should vaccine development ever become cavalier regarding RAS signaling and spike based agents