Synthetic Systems for Studying Natural Cells

         

Natural systems are heterogeneous and variable, complicating scientists' efforts to make sense of their observations. In contrast, synthetic systems provide a highly controllable platform for probing the natural world. To this end, scientists are creating lipid-based synthetic doppelgängers of cells and organelles to ask fundamental questions about biology. 

Oskar Staufer, a biophysicist at the Leibniz Institute for New Materials, uses synthetic biology to study cancer and the tumor immune environment. Cancer is a dysregulated system. The body loses control over proliferation and the immune environment surrounding the cell. “On a fundamental level, the idea is to regain control over the regulatory mechanisms within cancer cells,” said Staufer. This is where synthetic vesicles come into the picture. 

To generate these artificial structures, Staufer developed a microfluidic-based mechanical platform that divvies up a lipid cocktail into smaller water-in-oil droplets, or vesicles.¹  At approximately two micrometers in diameter, these synthetic vesicles are small enough to enter a cell but large enough to transport sizeable cargoes, such as high concentrations of an enzyme. 

To probe one element of cancer cell regulation, Staufer loaded his synthetic vesicles with an enzyme that reduces the levels of reactive oxygen species (ROS), signaling molecules that are abundant in cancer cells and shape the tumor microenvironment.^2,3 Then by tweaking the lipid composition and stiffness of the membrane, he created a vesicle that natural cells readily scoop up via endocytosis. Once inside the mammary gland-derived adenocarcinoma cell, shown in the above image in green, the synthetic vesicles, shown in magenta, reduced ROS levels, thus mimicking the natural functionality of peroxisomes, which are specialized organelles that carry out oxidative reactions. 

Synthetic vesicle technologies are still in their infancy, and Staufer noted, “We’re just trying to find out how the living and nonliving matter interact with each other.”