Entrainment of mammalian motile cilia in the brain with hydrodynamic forces

Abstract

Motile cilia are widespread across the animal and plant kingdoms, displaying complex collective dynamics central to their physiology. Their coordination mechanism is not generally understood, with previous work mainly focusing on algae and protists. We study here the entrainment of cilia beat in multiciliated cells from brain ventricles. The response to controlled oscillatory external flows shows that flows at a similar frequency to the actively beating cilia can entrain cilia oscillations. We find that the hydrodynamic forces required for this entrainment strongly depend on the number of cilia per cell. Cells with few cilia (up to five) can be entrained at flows comparable to cilia-driven flows, in contrast with what was recently observed in Chlamydomonas. Experimental trends are quantitatively described by a model that accounts for hydrodynamic screening of packed cilia and the chemomechanical energy efficiency of the flagellar beat. Simulations of a minimal model of cilia interacting hydrodynamically show the same trends observed in cilia.

Cilia density and flow velocity affect alignment of motile cilia from brain cells

“…Indeed, during the maturation period, the percentage of area covered by ciliated cells increases significantly as shown previously ( Guirao et al, 2010 ). In turn, higher cilia density promotes higher hydrodynamic screening of the external flow ( Pellicciotta et al, 2020 ), because less fluid can creep through a dense carpet of cilia. This hypothesis was demonstrated here in silico: our simulations show that densely packed cilia feel a lower average torque owing to the external flow, when their neighbours hydrodynamically screen them.…”

“…When cells were 70–80% confluent in T25 flasks, they were resuspended in Dulbecco's Modified Eagle's Medium (DMEM) with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin (P/S) at a concentration of 10 7 cell ml −1 ( Delgehyr et al, 2015 ). Then, cells were seeded in microfluidic Transwell chips ( Pellicciotta et al, 2020 ). This is a novel microfluid device composed of a PDMS channel bonded to the membrane of a Corning Transwell insert (CLS3450, Sigma-Aldrich) ( Pellicciotta et al, 2020 ).…”

“…Then, cells were seeded in microfluidic Transwell chips ( Pellicciotta et al, 2020 ). This is a novel microfluid device composed of a PDMS channel bonded to the membrane of a Corning Transwell insert (CLS3450, Sigma-Aldrich) ( Pellicciotta et al, 2020 ). These modified Corning inserts are placed in 6-well plates, and 2 ml DMEM medium supplemented with 10% FBS and 1% P/S is also added in the basolateral compartment.…”

“…These recent studies motivated us to investigate the time flow response of ependymal cell culture at shear stresses similar to that experienced in vivo . We exposed ependymal cells to shear stress in a novel microfluidic device composed of a PDMS channel, and standard Corning Insert recently developed in our group ( Pellicciotta et al, 2020 ). We found that cilia align with the external flow at all times in culture for shear stresses similar to the ones present in the brain.…”

Collective stiffening of soft hair assemblies

“…Soft hair assemblies are ubiquitous in biology [14]. Recently, Pellicciotta et al [27] have studied the collective beating of active motile cilia of brain cells subjected to oscillatory flows. They demonstrated an enhanced hydrodynamic screening with the number of cilia which reduces their synchronization with the external flow.…”