Novel Mechanism for Driving Amoeboid-Like Motility of Human Neutrophils under an Electric Field, Based on Intracellular Proton Currents and Cytoplasm Streaming

Abstract

Experimental studies have shown that actin filaments motion, cytoplasm streaming and muscle contraction can be reconstituted under actin-activated ATP hydrolysis by soluble non-filamentous myosin fragments. Thus, biological motility was demonstrated without requiring conventional contractile protein function. A possible alternative mechanism based on the integration of directional proton current and cytoplasm streaming is proposed to drive amoeboid-like cell motility and muscle contraction. To test the cell motility aspect of this mechanism, in the current study we employ a microfluidic device to quantitatively characterize human blood neutrophil electrotaxis. Several interesting predictions from this new model were confirmed in these experiments. We demonstrated firstly, the direct correlation of cytoplasm streaming to neutrophil motility profiles; secondly, the electric field and cell activation stage dependent directional neutrophil orientation and migration; and thirdly, the migration memory of neutrophil electrotaxis. These results support the importance of active intracellular force for driving amoeboid-like cell motility, with implications for physiological processes such as cell-cell migratory interactions and metabolic activation. This basic integrative working hypothesis is expected also to give raise to new applications in bioenergetics and immunological diagnosis and therapy.