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Molecular movement as a diagnostic tool

Scientists are developing diagnostic devices based on miniature cellular motors. Bio-engineered integration with molecules of interest and binding-induced motion may open the door to a new type of lab-on-a-chip.

Health

Molecular motors are protein machines in cells that move along cytoskeletal filaments (filaments that act like the cell's skeleton, giving it support and shape) using chemical energy from the hydrolysis of adenosine triphosphate (ATP). Among these is the myosin family, whose movement along actin filaments causes skeletal muscle to contract, helps transport intracellular cargo and plays a critical role in cell division. Scientists working on the EU-funded project 'Molecular motor-based nanodevices' (MONAD) are exploiting these ubiquitous cellular nanomachines in systems for diagnostics, drug discovery and basic biomedical research. Building on European expertise in molecular motors, MONAD is exploring the potential for quasi-immediate personalised diagnostics and the feasibility of future biosimulation devices. Biomolecular engineering techniques enabled demonstration of enhanced stability of actin filaments in the presence of tropomyosin, a family of muscle proteins that regulates the interaction between actin and myosin. In addition, scientists continued to optimise engineering of cytoskeletal filaments for detection. For example, bio-engineering filaments with antibodies will be used for detection of specific antigens. Deoxyribonucleic acid (DNA) or messenger ribonucleic acid (mRNA) will be used for ultra-sensitive diagnosis using disease markers. Studies of nanostructures with embedded molecular motors facilitated optimisation of control of motility on active surfaces. Focusing on applications to high-throughput drug screening of molecular activity, the team continued to identify motor binding sites that could be potent activators of motor proteins and have delivered several versions of a motility assay-based drug discovery device (based on activation leading to motion). Investigators are studying mathematical networks for use in designing biocomputation or biosimulation devices. Both network models have been tested with microtubules, actin filaments and bacteria. In addition, the team has established the experimental setup for studying motility assays as well as binding of target DNA or mRNA for development of ultra-sensitive diagnostic devices. Diagnostic capabilities of the MONAD technology will no doubt make the biggest market impact initially, although drug discovery of neuromuscular disease and biosimulation will also benefit substantially. In addition, knowledge generated will help maintain the competitive position of European research in the exciting field of molecular motors.

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