bioRxiv Science⌕ Search

Biology subjects

Esser, T. U.

Publications and source records attributed to Esser, T. U..

3 recordsLinked to original sources

Contractility of cardiac and skeletal muscle tissue increases with environmental stiffness

The mechanical interplay between contractility and mechanosensing in striated muscles is of fundamental importance for tissue morphogenesis, load adaptation, and disease progression, but remains poorly understood. In this study, we investigate the dependence of contractile force generation of cardiac and skeletal muscle on environmental stiffness. Using in vitro engineered muscle micro-tissues that are attached to flexible elastic pillars, we vary the stiffness of the microenvironment over three orders of magnitude and study its effect on contractility. We find that the active contractile force upon electrical stimulation of both cardiac and skeletal micro-tissues increases with environmental stiffness according to a strong power-law relationship. To explore the role of adhesion-mediated mechanotransduction processes, we deplete the focal adhesion protein {beta}-parvin in skeletal micro-tissues. This reduces the absolute contractile force but leaves the mechanoresponsiveness unaffected. Our findings highlight the influence of external stiffness on the adaptive behavior of muscle tissue and shed light on the complex mechanoadaptation processes in striated muscle.

biophysics↗

Direct 3D-bioprinting of hiPSC-derived cardiomyocytes to generate functional cardiac tissues

3D-bioprinting is a promising technology to produce human tissues as drug screening tool or for organ repair. However, direct printing of living cells has proven difficult. Here, we present a method to directly 3D-bioprint human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes embedded in a collagen-hyaluronic acid ink generating centimeter-sized functional ring- and ventricle-shaped cardiac tissues in an accurate and reproducible manner. The printed tissues contained hiPSC-derived cardiomyocytes with well-organized sarcomeres and exhibited spontaneous and regular contractions, which persisted for several months and were able to contract against passive resistance. Importantly, beating frequencies of the printed cardiac tissues could be modulated by pharmacological stimulation. This approach opens up new possibilities for generating complex functional cardiac tissues as models for advanced drug screening or as tissue grafts for organ repair or replacement.

bioengineering↗

MicroRNA-449 sustains cilia-related networks in the absence of transcription factor TAp73

Motile cilia serve vital functions in development, homeostasis and regeneration. We recently demonstrated that TAp73 is an essential transcriptional regulator of respiratory motile multiciliogenesis. Here, we show that TAp73 is expressed in multiciliated cells (MCCs) of diverse tissues. Analysis of TAp73-/- animals revealed that TAp73 regulates Foxj1, Rfx2, Rfx3, axonemal dyneins Dnali1 and Dnai1, plays a pivotal role in the generation of MCCs in reproductive ducts, and contributes to fertility. However, in the brain the function of MCCs appears to be preserved upon loss of TAp73, and robust activity from cilia-related networks is maintained in TAp73-/-. Consistent with TAp73-/-, its target miR34bc was reduced, whereas strong and specific induction of miR449 was observed along with an increase in E2f4, that induced transcriptional response from miR449 genomic regions. Depletion of both TAp73 and miR449 resulted in defective multiciliogenesis in the brain and hydrocephalus, indicating that miR449 and potentially additional pro-ciliogenic factors cooperate with TAp73 to ensure brain multiciliogenesis and CP development.

cell biology↗