A week in a viscous medium temporarily strengthened cultured T cells’ response to a chemical signal in older donors
A week in a viscous medium temporarily strengthened cultured T cells’ response to a chemical signal in older donors
A study published on October 15 in Nature Communications examined laboratory-activated T cells from 43 healthy donors aged 18–93. The researchers investigated how age affects cell movement when cells need to detect a chemical signal and squeeze through a narrow channel.
T cells moving through tissue detect local chemical signals and pass through tight spaces between other cells. Under a thin collagen gel, cells from younger and older donors had comparable mean speeds, displacement over an hour, and trajectory straightness. Differences emerged in channels 3 micrometers wide, where cells have to change shape to pass through.
At the channel exit, the authors established a gradient of SDF-1α, a chemokine that provides a molecular guidance cue for T cells. Cells from younger donors moved toward it at about 10 micrometers per minute and maintained their direction for longer. Cells from older donors responded less strongly; experiments with fluid flow and observations of changes in cell shape showed that these cells had more difficulty deforming.
The activated cells were then cultured for a week in a medium thickened with methylcellulose, with a viscosity of 8 centipoise rather than the usual 0,77. The cells were washed, returned to the standard medium, and tested again in the channels. In the main experiment, which involved 160 cells from six donors, cells from the older group reached the same speed and directional persistence toward SDF-1α as cells from younger donors. The effect persisted the next day, but by the fourth day these measures had returned to baseline.
After a week in the viscous medium, the cells had more CXCR4, the receptor that recognizes SDF-1α, and more F-actin, the filaments of actin protein beneath the membrane. Levels of Arp3, a protein involved in assembling the branched actin network, also increased. The authors also measured higher cell membrane tension. In treated cells from older donors, inhibiting either contractility or the activity of the Arp2/3 complex, which remodels actin filaments, returned speed and directional persistence to baseline.