Microengineered Ratchet Patterns in Nanowire Magnetoscope for Directing Rotational Bias and Programmed Cell Live/Death

Description

Mechanical cues from microenvironment regulate diverse forms of cell physiology. Forexample, it may direct programmed cell live/death, by which dissolution of extracellularmatrix (ECM) proteins promotes capillary involution in the formation of branchingnetworks. Recently, our group has discovered that cells can exert a new type of force –torque. This cellular torque has an intrinsic rotational bias, i.e. clockwise orcounterclockwise, depending on cell types. Similar to other cellular force, this biasedtorque may also couple with a type of environmental cues and potentially regulate themechanics-related physiology. However, due to the lack of appropriate platform, thishypothesis remains greatly unknown.Emerging evidences shows that the rotational bias is related to a swirl pattern of actinfilament anchored on ECM proteins, suggesting that a one-way ratchet pattern of ECMproteins may provide a mechanical cue to enhance or reverse the intrinsic rotational biasof cells. Based on this rationale, we will 1) construct a nanowire magnetoscopeintegrating the one-way ratchet pattern of ECM proteins to 2) characterize themodulated rotation and torque of cells for 3) exploring the dependence of programmedcell live/death. First, we will build the nanowire magnetoscope and fabricate the one-wayratchet patterns of ECM proteins through photolithography. Second, by culturingNIH 3T3 fibroblasts in the system, we will evaluate the change of rotational bias of cellsbased on the torque measurement and nucleus rotation. Meanwhile, actin cytoskeletonon the ratchet patterns will be analyzed to explore the potential change of the chiralalignment. Moreover, we will also explore whether the induced rotational bias of cells, ifexists, can be “memorized” when the mechanical cues from ratchet patterns issubsequently removed, addressing a possibility of prolonged influence of rotational cuein cell’s fate. At last, we will evaluate cell viability in response to the induced rotationalbias using MTS assay and live/death assay. It is to provide a potential associationbetween cell’s rotational bias and the programmed cell live/death important for tissuemorphogenesis. Together, this integrated platform combining ratchet patterns andnanowire magnetoscope will offer a valuable tool for understanding how rotational cuesfrom environment is coupled with the cells’ intrinsic rotational bias, opening up a newdimension in mechanotransduction in the future.?