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Betterton, M. D.

Publications and source records attributed to Betterton, M. D..

2 recordsLinked to original sources

Bound-state diffusion due to binding to flexible polymers in a selective biofilter

Selective biofilters are used by cells to control the transport of proteins, nucleic acids, and other macromolecules. Biological filters demonstrate both high specificity and rapid motion or high flux of proteins. In contrast, high flux comes at the expense of selectivity in many synthetic filters. Binding can lead to selective transport in systems in which the bound particle can diffuse, but the mechanisms that lead to bound diffusion remain unclear. Previous theory has proposed a molecular mechanism of bound-state mobility based only on transient binding to flexible polymers. However, this mechanism has not been directly tested in experiments. We demonstrate that bound mobility via tethered diffusion can be engineered into a synthetic gel using protein fragments derived from the nuclear pore complex. The resulting bound-state diffusion is quantitatively consistent with theory. Our results suggest that synthetic biological filters can be designed to to take advantage of tethered diffusion to give rapid, selective transport.\n\nSIGNIFICANCEBiological filters control the passage of proteins and other macromolecules between compartments of living systems. Determination of molecular mechanisms giving selective transport would enable the design of both selective filters and particles designed to penetrate biological barriers for drug delivery. One such mechanism arises from transient binding to dynamic polymer tethers. We designed a biomaterial which supports this type of tethered diffusion, demonstrating the potential to engineer bio-inspired filters.

biophysics

Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence. Large spindle length fluctuations can occur when the kinetochore-microtubule attachment lifetime is long. The primary spindle force generators are kinesin-5 motors and crosslinkers in early mitosis, while interkinetochore stretch becomes important after biorientation. The same mechanisms that contribute to persistent biorientation lead to segregation of chromosomes to the poles after anaphase onset. This model therefore provides a framework to interrogate key requirements for robust chromosome biorientation, spindle length regulation, and force generation in the spindle.

cell biology