9/23/2024 Taylor Parks 4 min read
Written by Taylor Parks
MechSE Assistant Professor Jie Feng and doctoral student Vinit Malik recently published work in Advanced Science with their collaborator, Associate Professor On Shun Pak (Santa Clara University). Their study, “Curvature-Assisted Vesicle Explosion Under Light-Induced Asymmetric Oxidation,” focused on conducting experiments and modeling to better understand vesicle dynamics under nonequilibrium conditions.
Biological vesicles are tiny organic compartments made from lipid molecules. Lipids, or fats, represent the most abundant component of the membrane in living cells. Vesicles occur naturally in human cells as storage for enzymes.
The exposure of biological cells to stressors such as radiation, pollutants, and heavy metals can cause lipids to oxidize. The oxidation process can drastically change the lipids’ physiochemical properties to the point of impeding homeostasis, or the self-regulating process by which biological systems maintain stability while continuously adapting for optimal survival. Indeed, oxidation can even result in vesicle explosion.
However, controlled vesicle explosion could be leveraged for the effective delivery of microscopic payloads in both industrial and biological processes.
“The vesicles we work with are roughly the diameter of one fifth of the width of a human hair,” Malik said. “These vesicles can be used to package small amounts of materials, which has a lot of promise for use in the human body. For example, drugs that are cytotoxic, like cancer drugs, could be packaged in a vesicle that is harmless to the body and delivered to cancerous tissue without killing healthy cells along the way.”
While other research studies have observed vesicles explode, these studies have not been able to pinpoint an explanation for the explosion. To investigate this phenomenon, the researchers fabricated vesicles from fluorescent lipid molecules and packaged them with photosensitizer molecules. They then exposed the vesicles to light to activate the photosensitizers, resulting in the production of highly reactive oxygen.
When photosensitizers were packed inside the vesicle membrane, the membrane’s inner layer oxidized much more rapidly than its outer layer. The reverse was true when photosensitizers were only present outside the membrane. Changes in shape during these processes were tracked using a fluorescent microscope. In both situations, the vesicle exploded.
“We found that when the shape of the lipid molecules is changed, the preferred curvature of the membrane changes; this preferred curvature is what we call spontaneous curvature,” Malik explained. “When the spontaneous curvature changes drastically enough, the membrane loses integrity and suddenly explodes.”
To verify that asymmetric-oxidation-induced spontaneous curvature was causing the vesicle explosion, the researchers packed photosensitizers on both sides of the membrane so that the inner and outer layers would oxidize at the same rate.
“We didn’t see any explosions, meaning that there was something special about oxidation happening asymmetrically,” Malik said.
“Our work highlights the previously unrecognized role of spontaneous curvature, generated through oxidation-induced conformational changes, in determining the fate of the vesicles,” Feng said. “Our framework offers valuable insights toward understanding the stability of inherently asymmetric biological membranes subject to oxidative assault, and can be used to guide the design of vesicle-based precision drug delivery systems.”
The researchers’ next step will be to investigate the use of magnetic microswimmers encapsulated in vesicles as a means of driving vesicle motion through the body for effective drug delivery. The team intends to develop general principles of vesicle movement for capillary systems.
Their published study was supported by the National Science Foundation under grant CBET 2323045.