Maren Romeyke

A step stress deforming suspended cells causes a passive relaxation, due to a transiently cross-linked isotropic actin cortex underlying the cellular membrane. The fluid-to-solid transition occurs at a relaxation time coinciding with unbinding times of actin cross-linking proteins. Elastic contributions from slowly relaxing entangled filaments are negligible. The symmetric geometry of suspended cells ensures minimal statistical variability in their viscoelastic properties in contrast with adherent cells and thus is defining for different cell types. Mechanical stimuli on time scales of minutes trigger active structural responses.

The cytoskeleton of an eukaryotic cell is a composite polymer material with unique structural (mechanical) properties. To investigate the role of individual cytoskeletal polymers in the deformation response of a cell to an external force (stress), we created two structural models - a thick shell model for the actin cortex, and a three-layered model for the whole cell. These structural models for a cell are based on data obtained by deforming suspended cells, where each cell is stretched between two counter-propagating laser beams using an optical stretcher. Our models, with the data, suggest that the outer actin cortex is the main determinant of the structural response of the cell.

Even minute alterations in a cell's intracellular scaffolds, i.e. the cytoskeleton, which organize a cell, result in significant changes in a cell's elastic strength since the cytoskeletal mechanics nonlinearly amplify these alterations. Light has been used to observe cells since Leeuwenhoek's times and novel techniques in optical microscopy are frequently developed in biological physics. In contrast, with the optical stretcher we use the forces caused by light described by Maxwell's surface tensor to feel cells. Thus, the stretcher exemplifies the other type of biophotonic devices that do not image but manipulate cells. The optical stretcher uses optical surface forces to stretch cells between two opposing laser beams, while optical gradient forces, which are used in optical tweezers, play a minor role and only contribute to a stable trapping configuration. The combination of the optical stretcher's sensitivity and high throughput capacity make a cell's "optical stretchiness" an extremely precise parameter to distinguish different cell types. This avoids the use of expensive, often unspecific molecular cell markers. This technique applies particularly well to cells with dissimilar degrees of differentiation, as a cell's maturation correlates with an increase in cytoskeletal strength. Because malignant cells gradually dedifferentiate during the progression of cancer, the optical stretcher should allow, the direct staging from early dysplasia to metastasis of a tumor sample obtained by MRI-guided fine needle aspirations or cytobrushes. With two prototypes of a microfluidic optical stretcher at our hands, we prepare preclinical trials to study its potential in resolving breast tumors' progression towards metastasis. Since the optical stretcher represents a basic technology for cell recognition and sorting, an abundance of further biomedical applications can be envisioned.