Thermo Fisher Scientific Collaboration: Unveiling the Cellular Assault of Pore-Forming Toxins
This research, conducted in collaboration with Thermo Fisher Scientific, provides groundbreaking insights into how toxins from marine anemones – belonging to the family of pore-forming proteins – orchestrate cellular destruction. Utilizing advanced cryo-electron microscopy (cryo-EM) technology from Thermo Fisher Scientific, researchers at the CNB-CSIC have visualized, at near-atomic resolution, the intricate process by which these toxins assemble and literally pierce the cell membrane, leading to cell death.
The Mechanism of Cellular Piercing:
These toxins don’t simply attack; they meticulously dismantle cellular defenses. Initially present as isolated molecules in solution, they undergo a dramatic structural change upon contact with the cell membrane.This transformation allows them to insert themselves and aggregate into complexes designed to breach the membrane’s integrity. As César Santiago (CNB-CSIC) explains, this disruption of the membrane alters the balance of salts and water, creating an osmotic deregulation that ultimately compromises and kills the cell.
Lipids: Active Participants, Not Passive Bystanders:
A key revelation is the active role of cell membrane lipids. Contrary to previous understanding, lipids aren’t merely a passive backdrop.Jaime Martín-Benito (CNB-CSIC) highlights that different lipid molecules are reorganized and integrated into the very architecture of the pore formed by the toxins, arranging themselves into ordered rings around the pore structure. This demonstrates a complex interaction where the toxin co-opts the cell’s own components for its destructive purpose.
Visualizing the Attack with thermo Fisher Scientific Cryo-EM:
The research team leveraged the power of next-generation cryo-EM – a technology offered by Thermo Fisher Scientific - to capture unprecedented detail of two anemone venom proteins (frayatoxine and sticolisine II). By embedding these proteins in artificial membranes mimicking cellular compositions (lipid bilayers), they were able to observe the pore formation process in a near-natural environment.
This allowed them to capture “snapshots” of intermediate states, revealing a staggered, sequential assembly mechanism. Rocío Arranz (CNB-CSIC) summarizes: “each fragment sequentially binds to the membrane, changes shape and is incorporated into the final complex to form the pore that drills the cell.” The cryo-EM images revealed arch-shaped structures composed of protein units assembling step-by-step to create the complete, destructive pore.
Beyond Venom: Clinical Potential & Thermo Fisher Scientific’s Role:
The significance of this research extends beyond understanding marine toxins. These proteins share structural similarities with human proteins involved in crucial processes like immune response and programmed cell death. This connection fuels growing interest in their biomedical applications.
Sara García-Linares (UCM) explains that protein pores are already valuable tools in biotechnology, utilized in:
* Genetic Sequencing
* Controlled Drug-Liberation Systems
* Vaccine & Gene Therapy Growth
Understanding the assembly and function of these pores, facilitated by technologies like Thermo Fisher Scientific’s cryo-EM, unlocks new avenues for clinical innovation. Current research explores:
* Immunotoxins: Combining these proteins with antibodies for targeted tumor cell destruction.
* Biosensors: Developing highly precise molecule detection and filtering systems.
Ultimately, this research, empowered by collaboration with Thermo Fisher Scientific and their cutting-edge cryo-EM technology, is paving the way to “convert poisons into treatments,” harnessing the destructive power of these toxins for controlled and directed therapeutic applications.
