Creeping motion of a solid particle inside a spherical elastic cavity. II. Asymmetric motion

An analytical method is proposed for computing the low-Reynolds-number hydrodynamic mobility function of a small colloidal particle asymmetrically moving inside a large spherical elastic cavity, the membrane of which is endowed with resistance toward shear and bending. In conjunction with the results obtained in the first part [Daddi-Moussa-Ider, L\"{o}wen, and Gekle, Eur. Phys. J. E 41, 104 (2018)], in which the axisymmetric motion normal to the surface of an elastic cavity is investigated, the general motion for an arbitrary force direction can be addressed. The elastohydrodynamic problem is formulated and solved using the classic method of images through expressing the hydrodynamic flow fields as a multipole expansion involving higher-order derivatives of the free-space Green's function. In the quasi-steady limit, we demonstrate that the particle self-mobility function of a particle moving tangent to the surface of the cavity is larger than that predicted inside a rigid stationary cavity of equal size. This difference is justified by the fact that a stationary rigid cavity introduces additional hindrance to the translational motion of the encapsulated particle, resulting in a reduction of its hydrodynamic mobility. Furthermore, the motion of the cavity is investigated, revealing that the translational pair (composite) mobility, which linearly couples the velocity of the elastic cavity to the force exerted on the solid particle, is solely determined by membrane shear properties. Our analytical predictions are favorably compared with fully-resolved computer simulations based on a completed-double-layer boundary integral method.Comment: 14 pages, 4 figures. This is a pre-print of an article published in The European Physical Journal E. The final authenticated version is available online at: https://doi.org/10.1140/epje/i2019-11853-

Online Gaming and Personality: Explaining Gamers’ Cheating Intention

Cheating in online games poses a risk to game publishers, as it deters other gamers and reduces revenues. These facts make it essential for game publishers to understand ‘who’ in the sense of gamers with what personalities have cheating intentions. Building on psychology research, we draw on (a) the big five personality traits and (b) the dark triad personality traits to explain how these reflect gamers’ personalities and together lead to cheating intentions. Following a configurational approach (N=192), we reveal two configurations explaining high cheating intention and one explaining low cheating intention. We contribute to online gaming research by revealing that gamers with cheating intentions have specific personalities. We advance information systems (IS) personality research by combining broad and dark triad traits to explain divergent behavior like cheating

CYP35: Xenobiotically induced gene expression in the nematode Caenorhabditis elegans

Although over 80 cytochrome P450 (CYP) encoding genes have been identified in the genome of the nematode Caenorhabditis elegans very little is known about their involvement in biotransformation. This paper demonstrates a concentration-dependent relationship of C. elegans CYP35A1, A2, A5, and C1 gene expression in response to four organic xenobiotics, namely atrazine, PCB52, fluoranthene, and lansoprazole. The toxicity of these xenobiotics was determined using a reproduction assay. CYP-specific messenger RNA expression was analyzed by semi-quantitative RT-PCR resulting in a strongly increasing, concentration-dependent induction well below the EC50 for reproduction. For PCB52, approximately 0.5% of the EC50 induces a 2-fold increase of CYP35 gene expression. Using a double mutant and multiple RNAi of CYP35A/C it was possible to diminish the reproduction decline caused by PCB52 and fluoranthene.Peer Reviewe

Targeted RNase: Human Antibody-RNase-Fusions against CD30+ lymphomas

Die steigende Bedeutung der antikörperbasierten Krebstherapie spiegelt sich in der stark gestiegenen Anzahl in klinischen Studien befindlicher mAk wider. Zusätzlich stehen insbesondere Antikörperfusionen zur Funktionserweiterung im Mittelpunkt. Ein Forschungsschwerpunkt konzentriert sich auf den Einsatz von RNasen als Fusionspartner der mAk. Das Prinzip der mittels Antikörper zielgerichtet geleiteten RNasen (Targeted RNase, TR), beruht auf der antigenspezifischen Bindung an Oberflächenmarker von Tumoren, die zu rezeptorvermittelter Endozytose befähigt sind. Nach Internalisierung muss eine Translokation ins Zytoplasma erfolgen, um die katalytische Funktion der RNase zur Inhibition des Proteinsyntheseapparates zu ermöglichen. In der Arbeit wurde ein vollständig humanes Antikörper-RNase-Fusionsprotein erzeugt, das gegen den internalisierenden Tumormarker CD30 gerichtet ist. Als Bindungsdomäne der TR-Konstrukte wurden unterschiedliche Antikörperformate untersucht. Bei BIAcore- und FACS-Messungen stellte sich das scFv-Fc-Format mit einer Affinität von 9,8x10-10M gegenüber dem scFv- und IgG-Format als überlegen heraus. Bei der Untersuchung der Auswirkung von der Antikörper-RNase-Fusion auf die RNase Aktivität zeigte sich, dass die C-terminale Fusion der RNase an die Fc-Domäne des CD30-spezifischen scFv-Fc die geringste Beeinträchtigung der RNase Aktivität verursachte. Die humane pankreatische RNase war gegenüber zytoplasmatisch vorhandenen RNasen-Inhibitoren nicht sensitiv und eine Internalisierung des scFv-Fc-RNase-Konstruktes nach Bindung an CD30+ Karpas 299-Zellen wurde nachgewiesen. Das Wachstum dieser CD30+ Zellen mit einer IC50 von 3,3 nM gehemmt. Das erzeugte CD30-scFv-Fc-RNase-Fusionskonstrukt ist das erste vollständig humane TR-Konstrukt, das zur Behandlung von CD30+ Lymphomen dienen könnte. Das Spektrum an behandelbaren Krebserkrankungen kann im Rahmen des TR-Konzepts durch den Austausch des Antikörpers auf weitere internalisierende Tumormarker erweitert werden.The increasing number of monoclonal antibodies tested in clinical trials for cancer reflects the growing importance of antibody-based cancer therapies. In addition to mAbs, the focus of research shifts towards antibody fusion proteins to provide biological entities with additional functions. One of the main research areas concentrates on the usage of RNases for antibody fusion proteins. The principle is based on specific targeting of RNase (Targeted RNase, TR) to cell surface markers of tumors which are capable of receptor mediated endocytosis. The specificity is provided by the antibody. The binding and internalizaton of the TR is followed by its translocation into the cytoplasm to provide catalytic function of the RNase to inhibit the protein synthesis. The outcome of this work lead to the first fully human antibody-RNase fusion protein targeting the internalizing tumor marker CD30. Various antibody formats were evaluated as antigen specific binding domain in TR-constructs. Surface plasmon resonance and FACS analysis revealed the superiority of the scFv-Fc format with an apparent affinity of ~9,8x10-10M. Investigating effects of antibody-RNase fusion on the RNase activity lead to the conclusion that the C-terminal fusion of RNase to the Fc domain of CD30 specific scFv-Fc is only of minor influence for RNase activity. Moreover, in the context of the scFv-Fc-RNase fusion human pancreatic RNase was not sensitive to ubiquitous cytoplasmatic RNase-inhibitor. Internalization of the TR-molecules binding to CD30+ Karpas 299 cells was proven. Finally growth of the CD30+ cell line could be inhibited with an IC50 of 3,3nM. In summary, the generated CD30-scFv-Fc-RNase-fusion protein is the first fully human Targeted RNase construct possibly useful for treatment of CD30+ lymphomas. The TR concept can be expanded to treat further cancer types by exchanging the antigen binding domain for antibodies targeting different internalizing tumor markers

Membrane penetration and trapping of an active particle

The interaction between nano- or micro-sized particles and cell membranes is of crucial importance in many biological and biomedical applications such as drug and gene delivery to cells and tissues. During their cellular uptake, the particles can pass through cell membranes via passive endocytosis or by active penetration to reach a target cellular compartment or organelle. In this manuscript, we develop a simple model to describe the interaction of a self-driven spherical particle (moving through an effective constant active force) with a minimal membrane system, allowing for both penetration and trapping. We numerically calculate the state diagram of this system, the membrane shape, and its dynamics. In this context, we show that the active particle may either get trapped near the membrane or penetrates through it, where the membrane can either be permanently destroyed or recover its initial shape by self-healing. Additionally, we systematically derive a continuum description allowing to accurately predict most of our results analytically. This analytical theory helps identifying the generic aspects of our model, suggesting that most of its ingredients should apply to a broad range of membranes, from simple model systems composed of magnetic microparticles to lipid bilayers. Our results might be useful to predict mechanical properties of synthetic minimal membranes.Comment: 16 pages, 6 figures. Revised manuscript resubmitted to J. Chem. Phy