Heterogeneous T cell motility behaviors emerge from a coupling between speed and turning in vivo

T cells in vivo migrate primarily via undirected random walks, but it remains unresolved how these random walks generate an efficient search. Here, we use light sheet microscopy of T cells in the larval zebrafish as a model system to study motility across large populations of cells over hours in their native context. We show that cell-to-cell variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds, and seen in Mouse T cells and Dictyostelium. These results suggest that there is a single variable underlying ameboid cell motility that jointly controls speed and turning. This coupling explains behavioral heterogeneity in diverse systems and allows cells to access a broad range of length scales.

Dynamic organization of ATP and birefringent fibrils during free locomotion and galvanotaxis in the plasmodium of Physarum polycephalum.

Directed migration by a cell is a good phenomenon for studying intracellular coordination. Dynamic organization of both ATP and birefringent fibrils throughout the cell was studied in the multinuclear ameboid cell of the Physarum plasmodium during free locomotion and galvanotaxis. In a directionally migrating plasmodium, waves of ATP as well as thickness oscillations propagated from just inside the advancing front to the rear, and ATP concentration was high at the front on the average. In a DC electric field, locomotion was inhibited more strongly, ATP concentration decreased more, and birefringent fibrils were formed more abundantly at the anodal than at the cathodal side. Inside the cell there were a few undulations in the distributions of ATP and birefringent fibrils. In short, birefringent fibrils become abundant where ATP concentration decreases. The possible mechanism of the coordination in the directed migration and the implications of the scaling law are discussed.

IMMUNOFLUORESCENT STUDIES OF HUMAN CELL CULTURES AND CHICK EMBRYOS INOCULATED WITH THE AMEBOID CELL-"LIPOVIRUS" COMPLEX

Tissue culture cells of human origin (HeLa, Lich, and AV3) were inoculated with the AL complex. By immunofluorescent staining, AL complex antigen was detectable in the cytoplasm of infected cells as punctate fluorescent granules during the early stage and as homogeneous fluorescence during the late stage of infection. By combining fluorescence and phase-contrast microscopy, many infected cells with cytoplasmic AL complex antigen were shown to have a normal nuclear morphology indistinguishable from uninfected cells. Initiation of AL complex infection was interpreted as occurring by transfer of transmissible factor(s) from cell to cell by contact and mutiplication of such factor(s) therein. Chick embryos were susceptible to AL complex infection following allantoic or amniotic inoculations. Antigen and infectious AL complex were demonstrable in the liver, brain, intestines, lungs, and embryonic membranes. Further investigations on AL complex and its relation to human disease are suggested.

ON THE NATURE OF THE "LIPOVIRUS"

Experiments designed to elucidate the nature of the "lipovirus" are described. The development of characteristic nuclear lesions in human cells in vitro depended on the presence of an ameboid cell in the inoculum. The spatial separation of the ameboid cells from the human cells by a membrane filter 150 µ in thickness was sufficient to prevent the development of nuclear lesions. Nuclear lesions appeared to be the primary change of the affected human cells. This development of nuclear lesions was partially suppressed by FUDR and the suppression was reversed by thymidine. Time-lapse microcinematography showed that a 30 min intermittent contact between an ameboid cell and a human cell resulted in the retraction of both progenies of the human cell after a lapse of about 36 hr. Other human cells not in contact with the ameboid cell remained polygonal and continued to divide. Radioautography of the ameboid cell revealed the presence in the cytoplasm of thymidine-containing DNAse-sensitive materials. The development of antigens related to the ameboid cell within the cytoplasm of the human cell is described in the accompanying report (4).