Measuring the Transmembrane Registration of Lipid Domains in Droplet Interface Bilayers through Tensiometry.

Diverse collections of lipids self-assemble into domains within biological membranes, and these domains are typically organized in both the transverse and lateral directions of the membrane. The ability of the membrane to link these domains across the membrane's interior grants cells control over features on the external cellular surface. Numerous hypothesized factors drive the cross-membrane (or transverse) coupling of lipid domains.

Enhancing membrane-based soft materials with magnetic reconfiguration events.

Adaptive and bioinspired droplet-based materials are built using the droplet interface bilayer (DIB) technique, assembling networks of lipid membranes through adhered microdroplets. The properties of these lipid membranes are linked to the properties of the droplets forming the interface. Consequently, rearranging the relative positions of the droplets within the network will also alter the properties of the lipid membranes formed between them, modifying the transmembrane exchanges between neighboring compartments.

Studying the Mechanics of Membrane Permeabilization through Mechanoelectricity.

In this research, real-time monitoring of lipid membrane disruption is made possible by exploiting the dynamic properties of model lipid bilayers formed at oil-water interfaces. This involves tracking an electrical signal generated through rhythmic membrane perturbation translated into the adsorption and penetration of charged species within the membrane. Importantly, this allows for the detection of membrane surface interactions that occur prior to pore formation that may be otherwise undetected.

A skin-inspired soft material with directional mechanosensation.

Lessons about artificial sensor design may be taken from evolutionarily perfected physiological systems. Mechanosensory cells in human skin are exquisitely sensitive to gentle touch and enable us to distinguish objects of different stiffnesses and textures. These cells are embedded in soft epidermal layers of gel-like consistency.

Droplet-Based Membranous Soft Materials.

Inspired by the structure and functionality of natural cellular tissues, droplet interface bilayer (DIB)-based materials strategically combine model membrane assembly techniques and droplet microfluidics. These structures have shown promising results in applications ranging from biological computing to chemical microrobots. This Feature Article briefly explores recent advances in the areas of construction, manipulation, and functionalization of DIB networks; discusses their unique mechanics; and focuses on the contributions of our lab in the advancement of this platform.

Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer. Unlike other types of breast cancer that can be effectively treated by targeted therapies, no such targeted therapy exists for all TNBC patients. The ADAR1 enzyme carries out A-to-I editing of RNA to prevent sensing of endogenous double-stranded RNAs.

A new approach for investigating the response of lipid membranes to electrocompression by coupling droplet mechanics and membrane biophysics.

A new method for quantifying lipid-lipid interactions within biomimetic membranes undergoing electrocompression is demonstrated by coupling droplet mechanics and membrane biophysics. The membrane properties are varied by altering the lipid packing through the introduction of cholesterol. Pendant drop tensiometry is used to measure the lipid monolayer tension at an oil-water interface.

Photopolymerized microdomains in both lipid leaflets establish diffusive transport pathways across biomimetic membranes.

Controlled transport within a network of aqueous subcompartments provides a foundation for the construction of biologically-inspired materials. These materials are commonly assembled using the droplet interface bilayer (DIB) technique, adhering droplets together into a network of lipid membranes. DIB structures may be functionalized to generate conductive pathways by enhancing the permeability of pre-selected membranes, a strategy inspired by nature.

Reconfiguring droplet interface bilayer networks through sacrificial membranes.

The droplet interface bilayer platform allows for the fabrication of stimuli-responsive microfluidic materials, using phospholipids as an organic surfactant in water-in-oil mixtures. In this approach, lipid-coated droplets are adhered together in arranged networks, forming lipid bilayer membranes with embedded transporters and establishing selective exchange pathways between neighboring aqueous subcompartments. The resulting material is a biologically inspired droplet-based material that exhibits emergent properties wherein different droplets accomplish different functions, similar to multicellular organisms.

Hydrogel Microelectrodes for the Rapid, Reliable, and Repeatable Characterization of Lipid Membranes.

Model lipid bilayer membranes provide approximations of natural cellular membranes that may be formed in the laboratory to study their mechanics and interactions with the surrounding environment. A new approach for their formation is proposed here based on the self-assembly of lipid monolayers at oil-water interfaces, creating a lipid-coated hydrogel-tipped electrode that produces a stable lipid membrane on the surface when introduced to a lipid-coated aqueous droplet. Membrane formation using the hydrogel microelectrode is tested for a variety of lipids and oils.

Evaluation of bending modulus of lipid bilayers using undulation and orientation analysis.

In the current paper, phospholipid bilayers are modeled using coarse-grained molecular dynamics simulations with the MARTINI force field. The extracted molecular trajectories are analyzed using Fourier analysis of the undulations and orientation vectors to establish the differences between the two approaches for evaluating the bending modulus. The current work evaluates and extends the implementation of the Fourier analysis for molecular trajectories using a weighted horizon-based averaging approach.

Encapsulating Networks of Droplet Interface Bilayers in a Thermoreversible Organogel.

The development of membrane-based materials that exhibit the range and robustness of autonomic functions found in biological systems remains elusive. Droplet interface bilayers (DIBs) have been proposed as building blocks for such materials, owing to their simplicity, geometry, and capability for replicating cellular phenomena. Similar to how individual cells operate together to perform complex tasks and functions in tissues, networks of functionalized DIBs have been assembled in modular/scalable networks.

Ferrofluid-Based Droplet Interface Bilayer Networks.

Droplet interface bilayer (DIB) networks allow for the construction of stimuli-responsive, membrane-based materials. Traditionally used for studying cellular transport phenomena, the DIB technique has proven its practicality when creating structured droplet networks. These structures consist of aqueous compartments capable of exchanging their contents across membranous barriers in a regulated fashion via embedded biomolecules, thus approximating the activity of natural cellular systems.

Local retention of antibodies in vivo with an injectable film embedded with a fluorogen-activating protein.

Herein we report an injectable film by which antibodies can be localized in vivo. The system builds upon a bifunctional polypeptide consisting of a fluorogen-activating protein (FAP) and a β-fibrillizing peptide (βFP). The FAP domain generates fluorescence that reflects IgG binding sites conferred by Protein A/G (pAG) conjugated with the fluorogen malachite green (MG).

Multifunctional, Micropipette-based Method for Incorporation And Stimulation of Bacterial Mechanosensitive Ion Channels in Droplet Interface Bilayers.

MscL, a large conductance mechanosensitive channel (MSC), is a ubiquitous osmolyte release valve that helps bacteria survive abrupt hypo-osmotic shocks. It has been discovered and rigorously studied using the patch-clamp technique for almost three decades. Its basic role of translating tension applied to the cell membrane into permeability response makes it a strong candidate to function as a mechanoelectrical transducer in artificial membrane-based biomolecular devices.

Multiscale modeling of droplet interface bilayer membrane networks.

Droplet interface bilayer (DIB) networks are considered for the development of stimuli-responsive membrane-based materials inspired by cellular mechanics. These DIB networks are often modeled as combinations of electrical circuit analogues, creating complex networks of capacitors and resistors that mimic the biomolecular structures. These empirical models are capable of replicating data from electrophysiology experiments, but these models do not accurately capture the underlying physical phenomena and consequently do not allow for simulations of material functionalities beyond the voltage-clamp or current-clamp conditions.

Activation of bacterial channel MscL in mechanically stimulated droplet interface bilayers.

MscL, a stretch-activated channel, saves bacteria experiencing hypo-osmotic shocks from lysis. Its high conductance and controllable activation makes it a strong candidate to serve as a transducer in stimuli-responsive biomolecular materials. Droplet interface bilayers (DIBs), flexible insulating scaffolds for such materials, can be used as a new platform for incorporation and activation of MscL.

Modeling the proton sponge hypothesis: examining proton sponge effectiveness for enhancing intracellular gene delivery through multiscale modeling.

Dendrimers have been proposed as therapeutic gene delivery platforms. Their superior transfection efficiency is attributed to their ability to buffer the acidification of the endosome and attach to the nucleic acids. For effective transfection, the strategy is to synthesize novel dendrimers that optimize both of these traits, but the prediction of the buffering behavior in the endosome remains elusive.