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Biomedical subjects

Jacob J Schmidt

Publications and source records attributed to Jacob J Schmidt.

7 recordsLinked to original sources
PubMed2006

Evaluation of synthetic linear motor-molecule actuation energetics.

By applying atomic force microscope (AFM)-based force spectroscopy together with computational modeling in the form of molecular force-field simulations, we have determined quantitatively the actuation energetics of a synthetic motor-molecule. This multidisciplinary approach was performed on specifically designed, bistable, redox-controllable [2]rotaxanes to probe the steric and electrostatic interactions that dictate their mechanical switching at the single-molecule level. The fusion of experimental force spectroscopy and theoretical computational modeling has revealed that the repulsive electrostatic interaction, which is responsible for the molecular actuation, is as high as 65 kcal.mol(-1), a result that is supported by ab initio calculations.

Microscopy, Atomic Force↗
PubMed2006

Hydrogel-encapsulated lipid membranes.

We have encapsulated free-standing planar lipid membranes in a polymer hydrogel via in situ photopolymerization. These encapsulated membranes were measured to last at least 5 days and provided a stable environment for single-molecule measurements of incorporated alpha-hemolysin channel proteins. The translocation of single-stranded DNA through alpha-hemolysin incorporated into these encapsulated membranes is slowed over 100 times relative to that of the gel-free state. These stabilized membranes, therefore, have application to the single-molecule analysis of DNA as well as broader application to biomolecular sensors, membrane protein biophysical studies, and drug discovery.

Bacterial Toxins↗
PubMed2006

Automated formation of lipid-bilayer membranes in a microfluidic device.

Although membrane channel proteins are important to drug discovery and hold great promise as engineered nanopore sensing elements, their widespread application to these areas has been limited by difficulties in fabricating planar lipid-bilayer membranes. We present a method for forming these sub-5-nm-thick free-standing structures based on a self-assembly process driven by solvent extraction in a microfluidic channel. This facile automatable process forms high-quality membranes able to host channel proteins measurable at single-molecule conductance resolution.

Crystallization↗
PubMed2005

Transmembrane glycine zippers: physiological and pathological roles in membrane proteins.

We have observed a common sequence motif in membrane proteins, which we call a glycine zipper. Glycine zipper motifs are strongly overrepresented and conserved in membrane protein sequences, and mutations in glycine zipper motifs are deleterious to function in many cases. The glycine zipper has a significant structural impact, engendering a strong driving force for right-handed packing against a neighboring helix. Thus, the presence of a glycine zipper motif leads directly to testable structural hypotheses, particularly for a subclass of glycine zipper proteins that form channels. For example, we suggest that the membrane pores formed by the amyloid-beta peptide in vitro are constructed by glycine zipper packing and find that mutations in the glycine zipper motif block channel formation. Our findings highlight an important structural motif in a wide variety of normal and pathological processes.

Amino Acid Motifs↗
PubMed2005

Self-assembled microdevices driven by muscle.

Current procedures for manual extraction of mature muscle tissue in micromechanical structures are time consuming and can damage the living components. To overcome these limitations, we have devised a new system for assembling muscle-powered microdevices based on judicious manipulations of materials phases and interfaces. In this system, individual cells grow and self-assemble into muscle bundles that are integrated with micromechanical structures and can be controllably released to enable free movement. Having realized such an assembly with cardiomyocytes we demonstrate two potential applications: a force transducer able to characterize in situ the mechanical properties of muscle and a self-assembled hybrid (biotic/abiotic) microdevice that moves as a consequence of collective cooperative contraction of muscle bundles. Because the fabrication of silicon microdevices is independent of the subsequent assembly of muscle cells, this system is highly versatile and may lead to the integration of cells and tissues with a variety of other microstructures.

Acrylic Resins↗
PubMed2002

Control of a biomolecular motor-powered nanodevice with an engineered chemical switch.

The biophysical and biochemical properties of motor proteins have been well-studied, but these motors also show promise as mechanical components in hybrid nano-engineered systems. The cytoplasmic F(1) fragment of the adenosine triphosphate synthase (F1-ATPase) can function as an ATP-fuelled rotary motor and has been integrated into self-assembled nanomechanical systems as a mechanical actuator. Here we present the rational design, construction and analysis of a mutant F1-ATPase motor containing a metal-binding site that functions as a zinc-dependent, reversible on/off switch. Repeated cycles of zinc addition and removal by chelation result in inhibition and restoration, respectively, of both ATP hydrolysis and motor rotation of the mutant, but not of the wild-type F1 fragment. These results demonstrate the ability to engineer chemical regulation into a biomolecular motor and represent a critical step towards controlling integrated nanomechanical devices at the single-molecule level.

Actins↗