Constricted migration is associated with stable 3D genome structure differences in melanoma cells

To spread from a localized tumor, metastatic cancer cells must squeeze through constrictions that cause major nuclear deformations. Since chromosome structure affects nucleus stiffness, gene regulation and DNA repair, here we investigate how confined migration affects or is affected by 3D genome structure. Using melanoma (A375) cells, we identify phenotypic differences in cells that have undergone multiple rounds of constricted migration. These cells display a stably higher migration efficiency, elongated morphology, and differences in the distribution of Lamin A/C and heterochromatin. Using Hi-C, we observe differences in chromosome spatial compartmentalization specific to cells that have passed through constrictions and related alterations in expression of genes associated with migration and metastasis. These sequentially constricted cells also show more nuclear deformations and altered behavior in a 3D collagen matrix. Our observations reveal a relationship between chromosome structure changes, metastatic gene signatures, and the altered nuclear appearance of aggressive melanoma.

Local, transient tensile stress on the nuclear membrane causes membrane rupture

Cancer cell migration through narrow constrictions generates compressive stresses on the nucleus that deform it and cause rupture of nuclear membranes. Nuclear membrane rupture allows uncontrolled exchange between nuclear and cytoplasmic contents. Local tensile stresses can also cause nuclear deformations, but whether such deformations are accompanied by nuclear membrane rupture is unknown. Here we used a direct force probe to locally deform the nucleus by applying a transient tensile stress to the nuclear membrane. We found that a transient (∼0.2 s) deformation (∼1% projected area strain) in normal mammary epithelial cells (MCF-10A cells) was sufficient to cause rupture of the nuclear membrane. Nuclear membrane rupture scaled with the magnitude of nuclear deformation and the magnitude of applied tensile stress. Comparison of diffusive fluxes of nuclear probes between wild-type and lamin-depleted MCF-10A cells revealed that lamin A/C, but not lamin B2, protects the nuclear membranes against rupture from tensile stress. Our results suggest that transient nuclear deformations typically caused by local tensile stresses are sufficient to cause nuclear membrane rupture.

Pocket formula for nuclear deformations of actinides

We have formulated a pocket formula for quadrupole [Formula: see text], octupole [Formula: see text], hexadecapole [Formula: see text] and hexacontatetrapole [Formula: see text] deformation of the nuclear ground state of all isotopes of actinide nuclei (89 [Formula: see text] Z [Formula: see text] 103). This formula is first of its kind and produces a nuclear deformation of all isotopes actinide nuclei 89 [Formula: see text] Z [Formula: see text] 103 with simple inputs of Z and A. Hence, this formula is useful in the fields of nuclear physics to study the structure and interaction of nuclei.

A microfluidic device for characterizing nuclear deformations

A high-throughput microfluidic workflow allows rapid mechanical characterisation and phenotyping of the nuclear stress response in embryonic stem cells.