Publications

Mechanotransduction mediated by the tension in lipid membranes is a well-established paradigm. This has been studied largely in the context of the plasma membrane, but recent work shows that it applies also to endomembranes, and specifically to the nuclear envelope. Here, we review membrane tension-mediated mechanotransduction at the nuclear envelope by focusing on its two best characterized modes of action: the cytosolic phospholipase A2 (cPLA2) pathway, and nuclear pore dilation. We discuss the mechanisms involved and their physiological implications. Finally, we discuss how nuclear envelope tension can be controlled and measured, and how its properties enable mechanosensing with different context-dependency than that of the plasma membrane. These properties apply to cPLA2 and nuclear pore complexes but potentially also to many other mechanosensors yet to be discovered.

JTD Keywords: Arachidonic-acid release, Bone-formation, C2 domain, Cytosolic phospholipase a(2), Cytosolic phospholipase a2, Force, Lipid-binding domain, Mechanobiology, Membrane, Membrane tension, Monolayer surface pressure, Nuclear deformation, Nuclear envelope, Nuclear pore complex, Nuclear transport, Nucleus, Packing, Pore complex, Tension, Yap

Enzyme-powered micro- and nanomotors make use of biocatalysis to self-propel in aqueous media and hold immense promise for active and targeted drug delivery. Most (if not all) of these micro- and nanomotors described to date are fabricated using a commercially available enzyme, despite claims that some commercial preparations may not have a sufficiently high degree of purity for downstream applications. In this study, the purity of a commercial urease, an enzyme frequently used to power the motion of micro- and nanomotors, was evaluated and found to be impure. After separating the hexameric urease from the protein impurities by size-exclusion chromatography, the hexameric urease was subsequently characterized and used to functionalize hollow silica microcapsules. Micromotors loaded with purified urease were found to be 2.5 times more motile than the same micromotors loaded with unpurified urease, reaching average speeds of 5.5 ?m/s. After comparing a number of parameters, such as enzyme distribution, protein loading, and motor reusability, between micromotors functionalized with purified vs unpurified urease, it was concluded that protein purification was essential for optimal performance of the enzyme-powered micromotor.

JTD Keywords: canavalin, catalysis, delivery, dls, enhanced diffusion, enzyme, lipase immobilization, micromotors, self-propulsion, super-resolution microscopy, urease, Mesoporous silica nanoparticles, Micromotors, Super-resolution microscopy

We report lipase-based nanomotors that are capable of enhanced Brownian motion over long periods of time in triglyceride solution and of degrading triglyceride droplets that mimic “blood lipids”. We achieved about 40 min of enhanced diffusion of lipase-modified mesoporous silica nanoparticles (MSNPs) through a biocatalytic reaction between lipase and its corresponding water-soluble oil substrate (triacetin) as fuel, which resulted in an enhanced diffusion coefficient (ca. 50 % increase) at low triacetin concentration (<10 mm). Lipase not only serves as the power engine but also as a highly efficient cleaner for the triglyceride droplets (e.g., tributyrin) in PBS solution, which could yield potential biomedical applications, for example, for dealing with diseases related to the accumulation of triglycerides, or for environmental remediation, for example, for the degradation of oil spills.

JTD Keywords: Enzyme nanomotors, Lipase, Micromotors, Oil removal, Self-propulsion