Cell contact guidance via sensing anisotropy of network mechanical resistance.

Despite the ubiquitous importance of cell contact guidance, the signal-inducing contact guidance of mammalian cells in an aligned fibril network has defied elucidation. This is due to multiple interdependent signals that an aligned fibril network presents to cells, including, at least, anisotropy of adhesion, porosity, and mechanical resistance. By forming aligned fibrin gels with the same alignment strength, but cross-linked to different extents, the anisotropic mechanical resistance hypothesis of contact guidance was tested for human dermal fibroblasts. The cross-linking was shown to increase the mechanical resistance anisotropy, without detectable change in network microstructure and without change in cell adhesion to the cross-linked fibrin gel. This methodology thus isolated anisotropic mechanical resistance as a variable for fixed anisotropy of adhesion and porosity. The mechanical resistance anisotropy |Y*| -1 - |X*| -1 increased over fourfold in terms of the Fourier magnitudes of microbead displacement |X*| and |Y*| at the drive frequency with respect to alignment direction Y obtained by optical forces in active microrheology. Cells were found to exhibit stronger contact guidance in the cross-linked gels possessing greater mechanical resistance anisotropy: the cell anisotropy index based on the tensor of cell orientation, which has a range 0 to 1, increased by 18% with the fourfold increase in mechanical resistance anisotropy. We also show that modulation of adhesion via function-blocking antibodies can modulate the guidance response, suggesting a concomitant role of cell adhesion. These results indicate that fibroblasts can exhibit contact guidance in aligned fibril networks by sensing anisotropy of network mechanical resistance.

Lichen planus of the eyelids: a case report and review of the literature.

Lichen planus (LP) of the eyelid is an under-reportedmanifestation of a common inflammatory condition.To the best of our knowledge fewer than 20 cases ofeyelid LP have been described in the English literature.We report a case of a 29-year-old woman whopresented with 3-month history of bilateral eyelidpruritic violaceous papules and similar lesions on herchest and lower extremity. Histology examinationrevealed characteristic findings and a diagnosisof LP was established. This report further reviewsthe previously reported 18 cases and discussesmanagement strategies.

A case of vemurafenib-induced keratosis pilaris-like eruption.

Vemurafenib, a selective BRAF kinase inhibitor, is a new anti-cancer drug recently proven to improve survival in patients with metastatic melanoma harboring the BRAF V600E mutation. BRAF is one of three RAF kinases (ARAF, BRAF, CRAF) involved in the MAP kinase pathway. Mutations in BRAF are reported to be present in 40 to 70 percent of melanomas and in lower frequencies in various other malignancies. The BRAF V600E mutation is a specific valine to glutamic acid single substitution that constitutes 80 to 90 percent of reported BRAF mutations. Successful treatment of metastatic melanoma with vemurafenib is not without significant adverse effects. The most common toxic effects of this drug include rash, arthralgia, and fatigue. Less commonly, cases of follicular cystic lesions, keratoacanthoma, and squamous cell carcinoma have also been described. We report a case of a patient with metastatic melanoma treated with vemurafenib, who developed diffuse follicular hyperkeratosis resembling keratosis pilaris. To our knowledge, this is the first reported case of a keratosis pilaris-like side effect of vemurafenib.