dichroism (CD) (Triba et al. 2006; McKibbin et al. 2007, 2009), as a vehicle to deliver a MP to oocyte
membranes (Kang et al. 2010) and as the recipient surfactant in MP cell-free synthesis (Lyukmanova
et al. 2011; Uhlemann et al. 2012) (cf. Chap. 7). Bicelles also have applications in galenics (see Dürr
et al. 2012, 2013, and references therein).
3.3
Nanodiscs
Nanodiscs (NDs) are arguably the most important original contribution made to the handling of MPs in
aqueous solutions over the past 20 years. Although their inception has a totally different origin from
that of bicelles, they are conceptually related. In both cases, the underlying idea was to provide MPs
with a bilayer environment while forming particles of nanometric dimensions. Bicelles, as recalled in
the preceding section, originated from the study of the organization of the composite micelles formed
by mixtures of phospholipids and bile salts, which play a key role in digestion. NDs are an outcome of
basic studies on high-density lipoproteins (HDLs), which are natural vehicles for transporting lipids in
the blood and delivering them to cells. In a sense, human physiology, which has to cope with the
problem of transporting water-insoluble lipids in aqueous bodily fluids, has handed us two distinct
solutions to this problem, each of which has been adapted by membrane biochemists to their own ends.
Since its inception at the end of the 1990s (Carlson et al. 1997; Bayburt et al. 1998, 2002;
Denisov et al. 2004), the field of ND-based MP studies has become enormous, with, by the end of
2016, “over 550 publications that use the nanodisc technology to advance the understanding of MPs”
(Denisov and Sligar 2017). The goal of this section is not to provide an exhaustive overview of this
vast field, which has been covered in many reviews (see e.g. Nath et al. 2007; Borch and Hamann
2009; Ritchie et al. 2009; Bayburt and Sligar 2010; Popot 2010; Malhotra and Alder 2014; Denisov
and Sligar 2016). A recent review by Ilia G. Denisov and Stephen G. Sligar is particularly to be
commended for its exhaustiveness and the critical distance it strives to maintain (Denisov and Sligar
2017). The accent of the present section is put on the nature and properties of NDs as a MP
environment rather than on the results obtained using them, of which only a few examples will be
given. As is the case throughout this book as regards this and other surfactant systems, my objective is
to give the reader elements for pondering the advantages and limitations of NDs as tools to investigate
this or that particular biological problem.
3.3.1
High-Density Lipoproteins
The use of NDs for handling MPs in aqueous solutions emerged as a largely unforeseen outcome of
research carried out on HDL particles by Ana Jonas, Stephen G. Sligar, and colleagues (see Jonas et al.
1991, Carlson et al. 1997, and references therein). The mature HDL is a complex comprising a protein,
apolipoprotein A-I (apoA-I), present as two to seven copies per particle, often accompanied by other
proteins, which stabilizes and keeps water-soluble a cargo of phospholipids, cholesterol, cholesteryl
esters, and triglycerides. In its mature form, the complex has a globular shape (“spherical” HDL,
sHDL). How exactly the lipids and proteins are assembled has been the object of protracted research
and controversies and remains debated (for recent reviews, see Phillips 2013; Gogonea 2016). One of
the difficulties is that HDLs are highly malleable, and the number of protein molecules and their
arrangement in the particle adjust to the size of the lipid cargo so that different experiments can suggest
different models without any of them being de facto erroneous.
Of particular relevance to the development of NDs is the fact that the formation of HDL particles
starts with that of a so-called “nascent” form (nHDL), in which apolipoproteins (two to four apoA-I
3.3 Nanodiscs
105
membranes (Kang et al. 2010) and as the recipient surfactant in MP cell-free synthesis (Lyukmanova
et al. 2011; Uhlemann et al. 2012) (cf. Chap. 7). Bicelles also have applications in galenics (see Dürr
et al. 2012, 2013, and references therein).
3.3
Nanodiscs
Nanodiscs (NDs) are arguably the most important original contribution made to the handling of MPs in
aqueous solutions over the past 20 years. Although their inception has a totally different origin from
that of bicelles, they are conceptually related. In both cases, the underlying idea was to provide MPs
with a bilayer environment while forming particles of nanometric dimensions. Bicelles, as recalled in
the preceding section, originated from the study of the organization of the composite micelles formed
by mixtures of phospholipids and bile salts, which play a key role in digestion. NDs are an outcome of
basic studies on high-density lipoproteins (HDLs), which are natural vehicles for transporting lipids in
the blood and delivering them to cells. In a sense, human physiology, which has to cope with the
problem of transporting water-insoluble lipids in aqueous bodily fluids, has handed us two distinct
solutions to this problem, each of which has been adapted by membrane biochemists to their own ends.
Since its inception at the end of the 1990s (Carlson et al. 1997; Bayburt et al. 1998, 2002;
Denisov et al. 2004), the field of ND-based MP studies has become enormous, with, by the end of
2016, “over 550 publications that use the nanodisc technology to advance the understanding of MPs”
(Denisov and Sligar 2017). The goal of this section is not to provide an exhaustive overview of this
vast field, which has been covered in many reviews (see e.g. Nath et al. 2007; Borch and Hamann
2009; Ritchie et al. 2009; Bayburt and Sligar 2010; Popot 2010; Malhotra and Alder 2014; Denisov
and Sligar 2016). A recent review by Ilia G. Denisov and Stephen G. Sligar is particularly to be
commended for its exhaustiveness and the critical distance it strives to maintain (Denisov and Sligar
2017). The accent of the present section is put on the nature and properties of NDs as a MP
environment rather than on the results obtained using them, of which only a few examples will be
given. As is the case throughout this book as regards this and other surfactant systems, my objective is
to give the reader elements for pondering the advantages and limitations of NDs as tools to investigate
this or that particular biological problem.
3.3.1
High-Density Lipoproteins
The use of NDs for handling MPs in aqueous solutions emerged as a largely unforeseen outcome of
research carried out on HDL particles by Ana Jonas, Stephen G. Sligar, and colleagues (see Jonas et al.
1991, Carlson et al. 1997, and references therein). The mature HDL is a complex comprising a protein,
apolipoprotein A-I (apoA-I), present as two to seven copies per particle, often accompanied by other
proteins, which stabilizes and keeps water-soluble a cargo of phospholipids, cholesterol, cholesteryl
esters, and triglycerides. In its mature form, the complex has a globular shape (“spherical” HDL,
sHDL). How exactly the lipids and proteins are assembled has been the object of protracted research
and controversies and remains debated (for recent reviews, see Phillips 2013; Gogonea 2016). One of
the difficulties is that HDLs are highly malleable, and the number of protein molecules and their
arrangement in the particle adjust to the size of the lipid cargo so that different experiments can suggest
different models without any of them being de facto erroneous.
Of particular relevance to the development of NDs is the fact that the formation of HDL particles
starts with that of a so-called “nascent” form (nHDL), in which apolipoproteins (two to four apoA-I
3.3 Nanodiscs
105