The cellular response to plasma membrane disruption for nanomaterial delivery

Abstract

Delivery of nanomaterials into cells is of interest for fundamental cell biological research as well as for therapeutic and diagnostic purposes. One way of doing so is by physically disrupting the plasma membrane (PM). Several methods that exploit electrical, mechanical or optical cues have been conceived to temporarily disrupt the PM for intracellular delivery, with variable effects on cell viability. However, apart from acute cytotoxicity, subtler effects on cell physiology may occur as well. Their nature and timing vary with the severity of the insult and the efficiency of repair, but some may provoke permanent phenotypic alterations. With the growing palette of nanoscale delivery methods and applications, comes a need for an in-depth understanding of this cellular response. In this review, we summarize current knowledge about the chronology of cellular events that take place upon PM injury inflicted by different delivery methods. We also elaborate on their significance for cell homeostasis and cell fate. Based on the crucial nodes that govern cell fitness and functionality, we give directions for fine-tuning nano-delivery conditions.

Wrangling Actin Assemblies: Actin Ring Dynamics during Cell Wound Repair

“…The study of cell wound repair has considerable clinical relevance. Pharmaceutical delivery methods and technologies are a popular and growing field of research that relies heavily on an understanding of the fundamental mechanisms of local and reversible plasma membrane disruptions to design effective methods of drug delivery [ 137 , 138 , 139 ]. Understanding the full spectrum of molecular mechanisms underpinning cell wound repair will provide important new insights into the many critical cell behaviors and fundamental biological regulations that take place during cellular events in daily life, and in pathological states from infections to diseases/cancers.…”

Recent advances in single-cell subcellular sampling

“…However, extracting 90% of the cytoplasmic volume may affect the microenvironment of some cell types and could lead to morphological changes, which may alter gene expression programs in cells. 83 In addition to successful extraction, the aspirated volumes from the nucleus and cytoplasm were sufficient for transcript detection by RT-qPCR, corresponding to 0.01 pg of total cellular RNA. The authors also performed enzymatic assays on the cytoplasmic samples to demonstrate the integrity of extracted proteins and successfully measure apoptosis following treatment with staurosporine, a protein kinase inhibitor.…”

Chemical Plasma Membrane Perforation Generated by a Microfluidic Probe for Single-Cell Intracellular Protein Delivery

“…25 The plasma membrane will reseal after cargo has entered the cell through the pores due to repair mechanisms which depend on the cell type, pore size, and extracellular environment. 26 However, the membranedisruption-mediated approach may lead to inconsistent levels of plasma membrane injury among cells, with too little resulting in insufficient delivery and too much causing severe cell damage. 3 To overcome the weaknesses of existing macroscale intracellular delivery methods, such as cell activity and inconsistent delivery efficiency, microtechnology mainly based on a membrane-disruption-mediated mechanism has emerged as a promising solution.…”