In-frame deletion of SPECC1L microtubule association domain results in gain-of-function phenotypes affecting embryonic tissue movement and fusion events.

Patients with autosomal dominant SPECC1L variants show syndromic malformations, including hypertelorism, cleft palate and omphalocele. These SPECC1L variants largely cluster in the second coiled-coil domain (CCD2), which facilitates association with microtubules. To study SPECC1L function in mice, we first generated a null allele (Specc1lΔEx4) lacking the entire SPECC1L protein.

Isolation and Time-Lapse Imaging of Primary Mouse Embryonic Palatal Mesenchyme Cells to Analyze Collective Movement Attributes.

Development of the palate is a dynamic process, which involves vertical growth of bilateral palatal shelves next to the tongue followed by elevation and fusion above the tongue. Defects in this process lead to cleft palate, a common birth defect. Recent studies have shown that palatal shelf elevation involves a remodeling process that transforms the orientation of the shelf from a vertical to a horizontal one.

Noonan syndrome patient-specific induced cardiomyocyte model carrying SOS1 gene variant c.1654A>G.

Noonan syndrome (NS) is a dominant autosomal genetic disorder, associated with mutations in several genes that exhibit multisystem abnormal development including cardiac defects. NS associated with the Son of Sevenless homolog 1 (SOS1) gene mutation attributes to the development of cardiomyopathy and congenital heart defects. Since the treatment option for NS is very limited, an in vitro disease model with SOS1 gene mutation would be beneficial for exploring therapeutic possibilities for NS.

Multicellular contractility contributes to the emergence of mesothelioma nodules.

Malignant pleural mesothelioma (MPM) has an overall poor prognosis and unsatisfactory treatment options. MPM nodules, protruding into the pleural cavity may have growth and spreading dynamics distinct that of other solid tumors. We demonstrate that multicellular aggregates can develop spontaneously in the majority of tested MPM cell lines when cultured at high cell density.

Scalable Biomimetic Coaxial Aligned Nanofiber Cardiac Patch: A Potential Model for "Clinical Trials in a Dish".

Recent advances in cardiac tissue engineering have shown that human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in a three-dimensional (3D) micro-environment exhibit superior physiological characteristics compared with their two-dimensional (2D) counterparts. These 3D cultured hiPSC-CMs have been used for drug testing as well as cardiac repair applications. However, the fabrication of a cardiac scaffold with optimal biomechanical properties and high biocompatibility remains a challenge.

Viscoelastic Properties of ECM-Rich Embryonic Microenvironments.

The material properties of tissues and their mechanical state is an important factor in development, disease, regenerative medicine and tissue engineering. Here we describe a microrheological measurement technique utilizing aggregates of microinjected ferromagnetic nickel particles to probe the viscoelastic properties of embryonic tissues. Quail embryos were cultured in a plastic incubator chamber located at the center of two pairs of crossed electromagnets.

Assessment of temporal functional changes and miRNA profiling of human iPSC-derived cardiomyocytes.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been developed for cardiac cell transplantation studies more than a decade ago. In order to establish the hiPSC-CM-based platform as an autologous source for cardiac repair and drug toxicity, it is vital to understand the functionality of cardiomyocytes. Therefore, the goal of this study was to assess functional physiology, ultrastructural morphology, gene expression, and microRNA (miRNA) profiling at Wk-1, Wk-2 & Wk-4 in hiPSC-CMs in vitro.

Manipulation-free cultures of human iPSC-derived cardiomyocytes offer a novel screening method for cardiotoxicity.

Induced pluripotent stem cell (iPSC)-based cardiac regenerative medicine requires the efficient generation, structural soundness and proper functioning of mature cardiomyocytes, derived from the patient's somatic cells. The most important functional property of cardiomyocytes is the ability to contract. Currently available methods routinely used to test and quantify cardiomyocyte function involve techniques that are labor-intensive, invasive, require sophisticated instruments or can adversely affect cell vitality.

Optical-flow based non-invasive analysis of cardiomyocyte contractility.

Characterization of cardiomyocyte beat patterns is needed for quality control of cells intended for surgical injection as well as to establish phenotypes in disease modeling or toxicity studies. Optical-flow based analysis of videomicroscopic recordings offer a manipulation-free and efficient characterization of contractile cycles, an important characteristics of cardiomyocyte phenotype. We demonstrate that by appropriate computational analysis of optical flow data one can identify distinct contractile centers and distinguish active cell contractility from passive elastic tissue deformations.

Cell resolved, multiparticle model of plastic tissue deformations and morphogenesis.

We propose a three-dimensional mechanical model of embryonic tissue dynamics. Mechanically coupled adherent cells are represented as particles interconnected with elastic beams which can exert non-central forces and torques. Tissue plasticity is modeled by a stochastic process consisting of a connectivity change (addition or removal of a single link) followed by a complete relaxation to mechanical equilibrium.