We
report, for the first time, merely using a small amount of (0.039%
w/w) Zn(II) instead of very high concentration (25%–50% w/w)
of conventional cryoprotective agents (CPAs), i.e., glycerol, during
the cryopreservation of red blood cells (RBCs) can lead to a comparable
post-thaw recovery rate of ∼95% while avoiding the tedious
gradient washout process for the removal of CPA afterward. The result
is remarkable, since Zn(II) does not have the ice-controlling ability
reported to be critical for CPA. It benefits from its moderate interaction
with lipid molecules, facilitating the formation of small and dynamic
lipid clusters. Consequently, the membrane fluidity is maintained,
and the cells are resilient to osmotic and mechanical stresses during
cryopreservation. This study first reports the ion-specific effect
on stabilizing the cell membrane; meanwhile, reversibly tuning the
structure of biological samples against injuries during the cooling
and rewarming provides a new strategy for cryopreservation.