Nilofar Faruqui

Cicada-inspired cell-instructive nanopatterned arrays

Biocompatible surfaces hold key to a variety of biomedical problems that are directly related to the competition between host-tissue cell integration and bacterial colonisation. A saving solution to this is seen in the ability of cells to uniquely respond to physical cues on such surfaces thus prompting the search for cell-instructive nanoscale patterns. Here we introduce a generic rationale engineered into biocompatible, titanium, substrates to differentiate cell responses. The rationale is inspired by cicada wing surfaces that display bactericidal nanopillar patterns. The surfaces engineered in this study are titania (TiO2) nanowire arrays that are selectively bactericidal against motile bacteria, while capable of guiding mammalian cell proliferation according to the type of the array. The concept holds promise for clinically relevant materials capable of differential physico-mechanical responses to cellular adhesion.

Differentially Instructive Extracellular Protein Micro-nets

An ability to construct biological matter from the molecule up holds promise for applications ranging from smart materials to integrated biophysical models for synthetic biology. Biomolecular self-assembly is an efficient strategy for biomaterial construction which can be programmed to support desired function. A challenge remains in replicating the strategy synthetically, that is at will, and differentially, that is for a specific function at a given length scale. Here we introduce a self-assembly topology enabling a net-like architectural mimetic of native extracellular matrices capable of differential responses to cell adhesion--enhanced mammalian cell attachment and proliferation, and enhanced resistance to bacterial colonization--at the native sub-millimeter length scales. The biological performance of such protein micro-nets directly correlates with their morphological and chemical properties, offering thus an application model for differential extracellular matrices.

Diffusion of biologically relevant molecules through gel-like tissue scaffolds.

Encapsulation of living cells into gel‐like matrices that are capable of maintaining their viability over an extended time period is starting to play a major role in medicine in applications such as, cell‐based sensors, cellular therapy, and tissue engineering. The permeability of nutrients and waste products through these matrices is critical to their performance. In this article, we report a methodology for selecting scaffolds with different permeabilities and surface area/volume ratios that can be used to house a 3D cell aggregate. Such a system can be modeled if the consumption or production rates for metabolites and waste products, respectively and the diffusion coefficients of these solutes in culture medium and the encapsulating gel matrix are known. A transient finite volume mass diffusion model, based on Ficks law, is derived where the consumption of a solute by the cells is modeled through a source term. The results show that the “performance” of cell‐doped gel is critically dependent on the rate at which cells consume key molecules e.g., glucose. Pragmatically, the model also provides insight as to how many cells a given gel geometry and structure can support. The approach used applies to any porous structure where mass transport occurs through diffusion.

Antimicrobial peptide capsids of de novo design

The spread of bacterial resistance to antibiotics poses the need for antimicrobial discovery. With traditional search paradigms being exhausted, approaches that are altogether different from antibiotics may offer promising and creative solutions. Here, we introduce a de novo peptide topology that—by emulating the virus architecture—assembles into discrete antimicrobial capsids. Using the combination of high-resolution and real-time imaging, we demonstrate that these artificial capsids assemble as 20-nm hollow shells that attack bacterial membranes and upon landing on phospholipid bilayers instantaneously (seconds) convert into rapidly expanding pores causing membrane lysis (minutes). The designed capsids show broad antimicrobial activities, thus executing one primary function—they destroy bacteria on contact.With the growing threat of antibiotic resistance, unconventional approaches to antimicrobial discovery are needed. Here, the authors present a peptide topology that mimics virus architecture and assembles into antimicrobial capsids that disrupt bacterial membranes upon contact.

Tuneable poration: host defense peptides as sequence probes for antimicrobial mechanisms

The spread of antimicrobial resistance stimulates discovery strategies that place emphasis on mechanisms circumventing the drawbacks of traditional antibiotics and on agents that hit multiple targets. Host defense peptides (HDPs) are promising candidates in this regard. Here we demonstrate that a given HDP sequence intrinsically encodes for tuneable mechanisms of membrane disruption. Using an archetypal HDP (cecropin B) we show that subtle structural alterations convert antimicrobial mechanisms from native carpet-like scenarios to poration and non-porating membrane exfoliation. Such distinct mechanisms, studied using low- and high-resolution spectroscopy, nanoscale imaging and molecular dynamics simulations, all maintain strong antimicrobial effects, albeit with diminished activity against pathogens resistant to HDPs. The strategy offers an effective search paradigm for the sequence probing of discrete antimicrobial mechanisms within a single HDP.

Nano-mechanical single-cell sensing of cell–matrix contacts

Extracellular protein matrices provide a rigidity interface exhibiting nano-mechanical cues that guide cell growth and proliferation. Cells sense such cues using actin-rich filopodia extensions which encourage favourable cell-matrix contacts to recruit more actin-mediated local forces into forming stable focal adhesions. A challenge remains in identifying and measuring these local cellular forces and in establishing empirical relationships between them, cell adhesion and filopodia formation. Here we investigate such relationships using a micromanipulation system designed to operate at the time scale of focal contact dynamics, with the sample frequency of a force probe being 0.1 ms, and to apply and measure forces at nano-to-micro Newton ranges for individual mammalian cells. We explore correlations between cell biomechanics, cell-matrix attachment forces and the spread areas of adhered cells as well as their relative dependence on filopodia formation using synthetic protein matrices with a proven ability to induce enhanced filopodia numbers in adherent cells. This study offers a basis for engineering exploitable cell-matrix contacts in situ at the nanoscale and single-cell levels.