Project abstract 1: Impact of membrane-tethered polymers on lipid vesicle mechanics (Kevin Jahnke)
The biophysical properties of lipid vesicles are important for their stability and integrity; they are also important for controlling the performance when these vesicles are used for drug delivery.
Generally, the vesicle properties are determined by the composition of lipids used to form the vesicle. However, for a given lipid composition, they can also be tailored by tethering of polymers to the membrane. We develop a general method to functionalize lipid vesicles with synthetic polymers and polysaccharides and incorporate them on the outer membrane leaflet of giant unilamellar vesicles (GUVs). We investigate their effect on membrane mechanics using micropipette aspiration and membrane fluidity using fluorescence recovery after photobleaching.
The results provide the potential means to study membrane-bound meshworks of polysaccharides similar to the cellular glycocalyx; moreover, they can be used for tuning the mechanical properties of drug delivery vehicles.
Project abstract 2: Engineering liposomes and lipid nanoparticles for drug delivery (Kevin Jahnke, Chenjing Yang, Chunhuan Liu, Tiffany Chen)
The successful delivery of nucleic acids to cells is an important way to fight disease.
It critically depends on the biophysical and chemical properties of the drug delivery vehicle. Liposomes and lipid nanoparticles are often employed as drug delivery vehicles because their properties can be meticulously fine-tuned. However, the search for the best possible modification for an efficient delivery is still ongoing.
We functionalize the outer leaflet of the drug delivery vehicles with different polymers and investigate their effect on cellular uptake and transfection. The polymers encompass a wide range of properties that can affect the performance of the drug delivery vehicles.
This work is a stepping stone for the development of more efficient drug delivery vehicles using controlled modifications. It also provides the means for the targeted delivery of drugs to specific cell types via polymer recognition.
Project abstract 3: Silk hydrogel formation within microfluidic droplets (Kevin Jahnke)
Silk hydrogels are important for cosmetics, drug delivery and tissue engineering. We encapsulate silk fibroin into surfactant-stabilized water-in-oil droplets to study the kinetics of their formation. Droplet-based microfluidics allows a high-throughput screening of silk hydrogel formation inside individual compartments. Within one day at room temperature silk fibroin aggregates and forms a hydrogel. We study the particle size via the droplet diameter, silk fibroin concentration or ethanol content in the aqueous phase to complement our understanding of the gelation process.
Project abstract 4: Microfluidic determination of lipid vesicle stiffness (Wenyun Wang, Kevin Jahnke)
The stiffness of lipid vesicles is important for engineering drug delivery vehicles and gaining fundamental insights into membrane biophysics. However, the determination of vesicle stiffness is mainly limited to three techniques: fluctuation spectroscopy, electrodeformation and micropipette aspiration. These suffer from very low throughput and lab-to-lab differences, which impedes a generalized and accepted catalogue of lipid vesicle bending rigidities and stretching moduli. We use microfluidics to develop a platform for the high-throughput screening of the mechanical properties of lipid vesicles. This will allow a standardized comparison between lipid compositions and decipher the impact of individual lipids on vesicle stiffness.
Project abstract 5: Photodegradable capsules for local cargo delivery (Wentao Xu, Kevin Jahnke)
The spatiotemporal control over the release of drugs is essential for investigating local responses of cells to chemical cues. However, classical methods like microneedles require to actively interfere with the sample, are low in throughput and cannot be used for 3D-tissues like organoids. Here, we employ microfluidics to form microcapsules that can be added to cell monolayers or tissues and locally degraded using light as a non-invasive external stimulus. Upon their degradation, they release their cargo which can then be taken up by cells. We use this approach to study the local response of cells in real-time. Moreover, we engineer capsules to induce apoptosis with full spatiotemporal control.
Contact：kjahnke@g.harvard.edu