Abstract

X-rays are widely used in mammography and radiotherapy of breast cancer. The research has focused on the effects of X-rays on cells in breast tissues, instead of the tissues' nonliving material, extracellular matrix. It is unclear what the influence of X-ray irradiation is on the matrix's mechanical cues, known to regulate malignant cancer-cell behaviors. Here, we developed a technique based on magnetic microrheology that can quantify the influence of X-ray irradiation on matrix viscoelasticity––or (solid-like) elastic and (liquid-like) viscous characteristics––at cell-size scales. To model breast-tissue extracellular matrix, we used the primary component of the tissue matrix, collagen type 1, as it is for control, and as irradiated by X-rays (tube voltage 50 kV). We used a magnetic microrheometer to measure collagen matrices using 10-μm-diameter magnetic probes. In each matrix, the probes were nanomanipulated using controlled magnetic forces by the microrheometer while the probes' displacements were detected to measure the viscoelasticity. The collagen-matrix data involve with a typical spatial variation in viscoelasticity. We find that higher irradiation doses (320 Gy) locally reduce stiffness (soften) collagen matrices and increase their loss tangent, indicating an elevated liquid-like nature. For lower, clinically relevant irradiation doses (54 Gy), we find insignificant matrix-viscoelasticity changes. We provide this irradiation-related technique for detection, and modification, of matrix viscoelastic cues at cell-size scales. The technique enables enhanced characterization of irradiated tissue constituents in a variety of breast-cancer radiotherapy types.

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