RESUMEN
Cytoplasmic dynein and kinesin-1 are microtubule-based motors with opposite polarity that transport a wide variety of cargo in eukaryotic cells. Many cellular cargos demonstrate bidirectional movement due to the presence of ensembles of dynein and kinesin, but are ultimately sorted with spatial and temporal precision. To investigate the mechanisms that coordinate motor ensemble behavior, we built a programmable synthetic cargo using three-dimensional DNA origami to which varying numbers of DNA oligonucleotide-linked motors could be attached, allowing for control of motor type, number, spacing, and orientation in vitro. In ensembles of one to seven identical-polarity motors, motor number had minimal affect on directional velocity, whereas ensembles of opposite-polarity motors engaged in a tug-of-war resolvable by disengaging one motor species.
Asunto(s)
Dineínas Citoplasmáticas/metabolismo , ADN/química , ADN/metabolismo , Cinesinas/metabolismo , Microtúbulos/metabolismo , Proteínas Motoras Moleculares/metabolismo , Dineínas Citoplasmáticas/química , ADN de Cadena Simple/química , ADN de Cadena Simple/metabolismo , Cinesinas/química , Quimografía , Proteínas Motoras Moleculares/química , Conformación de Ácido Nucleico , Multimerización de Proteína , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
In a previous report, we described heretofore undiscovered possibilities that neuropathic pain and spasticity may share some common pathophysiological mechanisms. Currently, systemically delivered local anesthetics are being used for the evaluation and treatment of neuropathic pain. We present a case describing the treatment of spasticity of spinal origin with continuous subcutaneous infusion of 0.75% bupivacaine in a patient who did not respond to traditional treatments and has become tolerant to intrathecal baclofen.
